Category Archives: Issue of the Month

EAS’s 2018 Year in Review and Expectations for 2019 – Evolving FSMA, Anticipation for TPMPs

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As we reflect on 2018, we are again honored that so many look to EAS as their regulatory solution to a complicated world of FDA requirements. FDA’s continued focus on safety as well as the industry’s embrace of regulations that often challenge their old methods of doing business can only mean continued improvements and communications in the name of public health. In 2018, the Food Safety Modernization Act (FSMA) again dominated the news as numerous compliance dates arrived. We received questions from all over the world, particularly on issues pertaining to the Foreign Supplier Verification Program (FSVP). As of June 1, 2018, FDA had completed 256 inspections of foreign firms resulting in the issuance of 483s. Based on that, one of the primary concerns our callers have is understanding what constitutes an FSVP in FDA’s eyes and whether their documentation or documentation they were in the process of preparing, would qualify as compliant. Questions on what is a Qualified Individual and how EAS can assist in that regard with foreign suppliers are also a concern.

Our Independent Advisor for FSMA, Charles Breen, stayed busy preparing updates on FSMA compliance as part of our EAS-e-News monthly column “FSMA Perspective” and he, as well as all of our consultants who work in Foods, collaborated on numerous webinars and articles helping the industry to gain a greater understanding of FDA expectations. We even conducted our first webinar in Spanish presented by Gustavo Gonzalez, Ph.D., “FSVP – What Does it Mean for Your Business?” which is available on-demand free of charge on the EAS website. More recently, Charles presented a webinar on FSVP for the National Customs Brokers and Forwarders Association of America.

It wasn’t just FSMA that got industry’s attention. New labeling regulations for food and dietary supplements have kept food and supplement manufacturers busy. From sugars to fibers to new requirements of what and how to include nutritional information, our Food Labeling and Dietary Supplement Labeling seminars have been very well attended. (Our spring series is scheduled for Philadelphia and hyperlinks here point to registration information should you be interested in joining us). In addition, EAS published articles on the subject and is pleased to be in the final preparation stages for a webinar on December 6th where James Hoadley, Ph.D. one of our expert labeling consultants and trainers will discuss the new dietary fiber regulations with two members of FDA’s CFSAN for the Institute for Food Technologists. These labeling issues are requiring firms to rethink how products are not only labeled but marketed and our Product Development and Labeling team is enjoying the challenge of helping firms navigate new requirements as they find solutions that meet both business and FDA expectations.

The dietary supplement industry continues to be challenged by GMPs dictated in 21 CFR 111 as evidenced by 2018 statistics indicating the top observations issued are still Specifications and Testing, Master Manufacturing Records and Batch Production Records, Quality Unit Responsibilities, and Complaints; the same as they have been since 2010 when the 21 CFR 111 regulations applied to all sizes of dietary supplement firms. Following is a graph prepared by the Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D., which summarizes the posted FDA statistics through 2017 and clearly illustrates this never-ending trend. If there is one bright spot, it is that the percentage of firms getting an Official Action Indicated (OAI) or Voluntary Action Indicated (VAI) is down to 54%. It has been significantly higher in previous years.

TOP FDA Observations: 2010 - 2017

RankCitationDescriptionNumber of Times Cited
201020112012201320142015201620172010-2017
121 CFR 111.75Testing541112262871881441952161421
221 CFR 111.70Specifications321041762342041542142511369
321 CFR 111.205MMRs28539411782678794622
421 CFR 111.255BPRs1852749371717287538
521 CFR 111.103QU Operations1843476647455576397
621 CFR 111.553Product Complaints1534427036283163319
721 CFR 111.453Holding & Distribrution618294732273046235
Total Observations631132819642211154912941625184212444

In medical devices, FDA’s decision to expand the use of the De Novo submission pathway was welcomed by industry. De Novo applications are appropriate in cases where it appears that the device meets the statutory standards for classification into Class I or Class II under section 513(a)(1) of the FD&C Act, and when the sponsor has determined that the device does not fall within any existing classification regulation. EAS authored an article for MedTech Intelligence on the subject.

EAS expanded its services into the area of cannabis GMPs in 2018. This newly evolving industry, regulated by some states as a food, others a dietary supplement and in some cases as a pharmaceutical, is challenged in many regards with how to set up, validate and verify a quality system. Quality is one of EAS’ many strong capabilities and our team of consultants is rising to the challenge of assisting this newer industry. Tara Couch presented a webinar “Quality Systems for the Cannabis Industry” and for the first time, we incorporated cannabis applicability into our two-day dietary supplement GMP seminar for a special presentation. We were also frequent contributors to the Cannabis Industry Journal including Gabe Miller who authored an article on Food Safety in the cannabis industry and Celia Schebella who discussed designing cannabis edibles in the state of California.

As we look ahead to 2019 there are a few notable things on the horizon that EAS consultants are watching for:

On the Tobacco front, the Center for Tobacco Products’ director Mitch Zeller, announced at the annual Tobacco Merchants Association (TMA) meeting that the agency is actively working on developing its own set of GMP protocols for the tobacco industry, called Tobacco Product Manufacturing Practices (TPMPs). In an effort to help tobacco firms begin forward thinking in these terms, EAS Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D. and President and COO, Dean Cirotta presented a webinar in partnership with TMA (now available on-demand) on how to prepare for these TPMPs based on the long-standing GMPs for the dietary supplement industry.

In addition, OTC Monograph reforms have been underway for some time and it is anticipated that 2019 will bring these new requirements to light. Independent Consultant Norma Skolnik prepared an article for EAS-e-News on expectations earlier in the year and EAS Independent Advisor for OTC Drugs and Labeling, Susan Crane, will present a five-part webinar series on the subject starting January 16. She’ll discuss why these reforms are necessary, are being undertaken now, and how OTC drug companies can expect those changes to impact their labels.

In the Dairy world, FDA has fast-tracked a review of how the words “milk” and “cheese” are used in dairy substitutes. The Dairy industry is also anticipating enforcement of the new Appendix T of the PMO which will implement FSMA-like requirements aimed at preventive measures to improve safety. More information on both of these as they unfold.

On the home office front, the EAS staff was very pleased when the extensive expansion and renovation of our office space was complete, and we think it looks great! This new area enables EAS training hosted in the DC area to move in-house and offers enhanced meeting capabilities, both in-person and remote. If you are in the D.C. area, we invite you to come by! In addition, we completed a major redesign of our website, found at easconsultinggroup.com. We hope you’ll agree that this new digital space is not only improved in appearance but provides easier access to not only information about EAS services and seminars, but also regulatory information prepared by our independent consultants and distributed through a variety of professional trade journals and organizations.

We also welcomed 24 new consultants, re-welcomed three consultants who returned to EAS after a stint in the industry and brought on a new office manager, Jodi Burns. EAS is only as strong as our professional network of skilled and knowledgeable consultants, directors and support staff. We feel we have some of the best in the business!

If it seems like EAS consultants have a wide-reach of educational support, you are right. All told EAS presented 13 two-day public seminars, will have conducted 19 webinars by the end of 2018; published 40 articles, and spoke or moderated at 25 industry events such as IFT, Food Safety Consortium, Supplyside West and a variety of FDLI-hosted events. We also exhibited at important trade shows such as IFT, Supplyside West, Food Defense Conference, IAFP and others.

One trade show event, nearest and dearest to our hearts was the 2018 AdvaMed MedTech Intelligence conference in Philadelphia where Ryan Steele, granddaughter of Chairman and CEO of Ed Steele, and daughter of CFO Brett Steele, was an invited speaker on the main stage sharing her story as just one many who has been positively impacted by the innovation of science and technology, in Ryan’s case with the implantation of a vertical expandable prosthetic titanium rib, which is the only FDA approved device to treat thoracic insufficiency syndrome.

It is stories such as hers that brings home why we all do what we do, designing products that fill a need and a niche and do so safely and effectively. While FDA regulations may feel cumbersome at times, it is those instances, where important decisions with critical outcomes are in front of us, that we can all appreciate FDA’s diligent focus on ensuring only compliant products are available to the US consumer. Here at EAS, we support firms working in all FDA regulated commodities to do just that and we take great pride in our ability to meet their needs.

Thank you for journeying with us in 2018 and we look forward to a peaceful and prosperous 2019. Have a very happy holiday and New Year!

Four Common Mistakes When Selecting a Rapid Method for Environmental Testing

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We are now firmly in the era of the Food Safety Modernization Act. It’s no longer theoretical, it’s real world, and FDA is auditing and asking questions about what they are seeing.

I think we can all agree on one thing. The way we looked at environmental pathogen testing in the past is out the window. Gone are the days of testing the same 10 sites every few months for generic Listeria and calling it good. Sometimes, you would get a hit and do an investigation, but that was the extent of the excitement.

You now need a robust program that looks at multiple pathogens and takes them all the way out to speciation. Some companies are even going further and developing a “microbiological map” of their processing areas. The technology is overwhelming, but one factor is still critical, and that’s time.

No one has the time to put all their product on hold while waiting for five days to a week for results. Of course, that assumes that nothing comes back as a presumptive positive. If it does, you can wait a few days longer while logistics breathes down your neck, and customers have empty shelves. What to do?

You need a new program to test for your environmental pathogens. But, how do you choose? Instead of evaluating the ever-changing landscape of tests available, it might be more useful to list four rules you need to follow for your decision-making process. This is an expensive decision, so make the right one as you are going to be living with it for a long time.

You need a fast turnaround, and in most cases, that means you are now considering something that wasn’t even possible in the past -testing samples and releasing in-house. The first step is to get out there and see the amazing new micro testing world that is at your fingertips.

  1. Don’t get sold by a fancy presentationYou begin your journey by attending a trade show and marveling at the technology available. You strike up a conversation with a salesperson and after ten minutes, you are convinced that this new whiz-bang machine is the wave of the future. If you place your order today, you can get a huge discount and get one of the few machines that are even available. You can also add in a low monthly payment program. It does everything you want, and more in an hour and costs pennies to operate. It’s amazing, and you are in love.Not so fast, partner. It’s just like when you buy a car. The salesman at the dealership does everything to move you toward a purchase. How? By using your emotions. People buy on emotion and use logic to rationalize their decision after the fact.

    The thing the salesman wants you to forget is that this is a commodity and another similar model is available just down the street. Remember, any attempt to pressure you into a purchase should be met with a knowing smile. The deal they quote is not a once in a lifetime opportunity, and it will be there once you have time to make a decision in the calm light of rational thought. Be cool, try to find a technical representative of the company to talk with in addition to the sales or marketing staff. Remember it’s a piece of equipment, and one that is equally as good or even better is just around the corner. Add this piece of equipment to your list of possible testing methods and move on down the trade show to the next one.

  2. Not using a validated methodologyThis goes with the first point. You need a method and technology that are approved for your application. It needs to be benchmarked back to reference methodologies. Has it been used on your product matrix? Peanut butter will likely react very differently to the test than yogurt. Everything on your list needs to clear these hurdles before you even consider it. Don’t accept “the approval will happen in two weeks” line or something similar. You are in control of the validation and benchmarking process and must have a test and equipment that hold up to regulatory scrutiny.Ask the following questions as you look at the candidates:
    1. Has it been validated for my product matrix by one of the following?
      • A recognized independent organization such as AOAC, AFNOR, MicroVal or
      • A US regulatory body (FSIS MLG, FDA BAM or an ISO Method?
    2. Is the method?
      • Fit for the purpose and application
      • Performed under validated conditions by a lab that assures the quality of analytical results

    These questions come from the USDA Food Safety Inspection Service. They have compiled a list of validated methods that you can use as a starting point. It’s forty-six pages long! Cross off any candidates that didn’t make your list, realizing that FDA utilizes the BAM as their reference for acceptable analytical methods.

  3. Not testing in-house before you buyNever, ever buy a new testing method without trying it out first – for a long period of time. Any reputable company will have a loaner machine you can use. If they balk, cross them off the list and move on.Decide if you can test as a group or one at a time. This is a question of resources and how many people can do what. Don’t use the results for actual product release. Keep that the same as you are doing now.Another good idea is to test at the point of use in the plants. Don’t test at the corporate lab. You lose too many variables that need to be accounted for at the plant.Test it with every permutation you can think of. Analyze enough samples so you can make sure the results are repeatable. Find out the limits of detection for your product. What are the false positive and false negative rates? What is the turnaround time for results? See if your technicians can screw up the test. Make your test as foolproof as you can.Also ask yourself: Can you get test supplies in a reasonable period of time? What is the minimum order quantity? What is the breakpoint for discounts? Are your supplies expiring before you can use them? Are there other uses for this equipment?This list is not inclusive by any stretch; its a starting point. Create the list and stick to it. Don’t change it as you go along as it will bias the results toward the newest test. Be consistent.Remember, you may need to defend the test results in court one day. This is the litmus test for acceptance that you must always keep in mind in the age of FSMA. Send back any that don’t make the cut and cross them off the list.
  4. Not researching the companyGreat! Your list is down to the top two testing methods. They are both reliable and repeatable, have fast turnaround time, dependability and a decent cost per test. How do you decide now?The test is only as good as the company supporting it. If they are new to the scene, will they be here in five years? Will they come up with a new test and abandon the old one, leaving you with an expensive paperweight? Do they have references you can talk to? Can you talk to references who have had challenges with the test?Are they willing to work with you on price? Can you get other perks such as free service calls? How will they support you and the warranty? Just like the test, you need a huge list of questions to hit them with.

Final Thoughts

Congratulations! This was a big decision, but you made the right one for you. The method and the test you selected are the cornerstones of your new environmental testing program. You are finding out where pathogens hide in your plant and eradicating them. You have a clear record of identification and correction that any auditor will be happy to review. You sleep easy at night knowing that you made the right decision, and you have the ability to defend it if you need to.

Be proud of your work and welcome to the new age of FSMA!

Reference: FSIS List of Foodborne Pathogen Test Kits Validated by independent Organizations

Legislation to Reform the OTC Drug Monograph System: The OTC Drug Safety, Innovation, and Reform Act

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With the aim of overhauling the regulation of over-the-counter (OTC) monograph drugs, U.S. Senators Johnny Isakson and Bob Casey recently sponsored bipartisan legislation, the Over-the-Counter Drug Safety, Innovation, and Reform Act of 2018, S.2315. The bill, which has already passed in the House of Representatives, was approved by the Senate Health, Education, Labor, and Pensions committee on April 24, 2018, and was received by the Senate at large on July 17, 2018. A previous bill, the Over-the-Counter Monograph Safety, Innovation, and Reform Act of 2017, authored by Representative Bob Latta (R-OR) and others, was introduced over a year ago.

As most people know, the current monograph system, which was implemented in 1972, has received much criticism and there have been several prior efforts to revise what’s been called an outdated “broken system”. The current monograph system’s drawbacks include the slow rulemaking process (many OTC drugs are marketed under incomplete monographs), the inability to swiftly and promptly address safety issues, and barriers to innovation (eligibility is largely limited to active ingredients that were marketed before 1972). In addition, FDA has acknowledged that it currently lacks the resources to effectively regulate all OTC monograph products.

The proposed bill is intended to speed up the current slow and time-consuming regulatory procedures by introducing the administrative order process to replace the current rulemaking procedures. It provides options for manufacturers to request administrative orders and for FDA to initiate administrative orders on its own initiative as well as in response to a citizens’ petition.

The S2315 bill would also establish a process for the introduction of new OTC products that are marketed without an approved New Drug Application. This legislation would authorize the agency to grant 2 years of product differentiation and exclusive market protection for certain qualifying OTC drugs, thus delaying the entry of other versions of the same qualifying OTC product.

The bill also includes provisions that would provide FDA with the authority to take rapid action in the event of safety issues with OTC drugs and requires that FDA re-evaluate the OTC cold and cough monograph with respect to children under the age of six and report annually to Congress on the progress of this evaluation. This was prompted by a 2007 internal review that linked the deaths of 54 children younger than 6 years to the use of OTC decongestants and cough medications.

Additionally, the new legislation will help manufacturers who wish to develop innovative products, for example, by adding new ingredients or creating new dosage forms of existing OTC drugs. It should provide a more streamlined regulatory pathway for review of innovations within the OTC Monograph system, accommodating marketplace innovations, such as new uses for ingredients, dosage forms, and other advancements. It should also provide a mechanism to encourage investment in data needed for significant innovations.

Reforming the OTC monograph system should benefit consumers and give FDA the resources that it needs to provide effective oversight of these widely used drug products.

The proposed legislation updates the monograph process by specifically adding a new section to the Federal Food, Drug, and Cosmetic Act (FFD & C) to implement the following:

  • Move away from the cumbersome current monograph finalization process to an “administrative order” procedure. The system for future changes to Monographs would be through the administrative order procedure with an opportunity for development meetings or other consultations, comment on proposed orders, and dispute resolution protections
  • Include by reference existing OTC Review Final Monographs and deem final all existing Tentative Final Monographs by statute
  • Create new pathways to innovation for monograph products, where none currently exits
  • Ensure that the new drug approval pathway and other nonprescription drugs otherwise lawfully marketed are not affected
  • Create a mechanism for faster OTC drug safety label changes;

Importantly, the bill provides FDA with the authority to collect user fees to help cover much of the costs of updating the regulatory system and provide the necessary resources to evaluate and monitor the OTC drug market. It’s hoped that the user fees will provide FDA with the funding and staff required to better oversee OTC drug compliance and build a critical IT/electronic infrastructure. This bill differs from previous versions because of its’ exclusivity provision.

The OTC Drug Safety, Innovation, and Reform Act is now awaiting Senate action. There is a great deal of bipartisan support for this bill, including from the American Academy of Allergy, Asthma & Immunology, the American Dental Association, and the American Academy of Pediatrics, who have urged passage because of the need to overhaul and modify pediatric dosing for OTC drugs, particularly OTC cough and cold drugs. It’s also been supported by the Consumer Healthcare Products Association (CHPA), the leading U.S. trade association representing OTC drug manufacturers and marketers. However, although it has widespread support and appears likely to pass, this is not a “must pass” bill like other existing user fee legislation. When it does pass, this legislation will have an enormous impact on the OTC drug industry in this country.

FDA Mutual Recognition Agreements

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FDA has been implementing the Safety and Innovation Act since it was passed by Congress in 2012. The Act requires FDA to establish Mutual Recognition Agreements (MRAs) which are agreements between two or more countries to recognize a specific process or procedure of the other country. The FDA’s MRA was preceded by the 1998 signing of the U.S. and the EU Agreement on Mutual Recognition which included a Pharmaceutical Annex providing for recognition of each other’s GMP inspections. Unfortunately, this Annex was never fully implemented.

Effective in 2017, the amended Sectoral Annex to the 1998 U.S.-EU MRA allowed for inspection reports and other related information obtained during drug manufacturing facility inspections, conducted by either an EU inspectorate or by FDA, to help determine whether a facility is manufacturing high-quality drugs. If more information is necessary beyond this assessment, FDA or the EU can then require additional inspections or take other action in the interest of protecting the public.

The 2017 Annex provides for greater efficiency in the drug inspection process, eliminating the redundancies of duplicate facility inspections, particularly those with a strong record of compliance. By utilizing each other’s inspection reports and related information, the FDA and EU are able to reallocate resources towards inspection of drug manufacturing facilities with potentially higher public health risks across the globe, benefiting patients and reducing adverse public health outcomes.

FDA’s determination as to whether an MRA is appropriate is made first via an assessment of internal audits in a particular EU country to ensure that their inspectorate is functioning properly and not deviating in any significant way from EU law and guidance.

These audits include observations of drug manufacturing facility inspections conducted by the audited inspectorates and utilize the 78 indicators based on the Pharmaceutical Inspection Co-operation Scheme (PIC/S) compliance assessment program with an EU addendum. PIC/S is an internationally recognized cooperative arrangement between 49 regulatory authorities, including the FDA. The goal of PIC/S is to harmonize inspection procedures worldwide and develop common standards in the field of good manufacturing practices.

In addition, FDA considers any conflict-of-interest policies, specific legislation related to good manufacturing practices, samples of inspection reports, inspector training records, inventory of drug manufacturing facilities, surveillance program, and numerous standard operating procedures to evaluate a pharmaceutical inspectors’ credentials as part of the capability assessment of each EU country. In this way, FDA can ascertain whether the inspection authorities are trained and qualified and have the skills and knowledge to identify manufacturing practices that may lead to patient harm. Maintenance provisions are also included in the Annex to ensure that each capable country continues to meet FDA requirements.

Thanks to this MRA, there is a greater ability of the Agency to appropriately allocate its resources to focus on those facilities where initial audits raise red flags that warrant further inspection, either by continual deficiencies in inspection findings by a country’s own internal audit system or by adverse events reports or other means. One of those means is the “Drug Quality Sampling and Testing (DQST)- Human Drugs Compliance Program 7356.008”, which is a surveillance program that samples and tests pharmaceutical products manufactured both in the U.S. and foreign countries. Surveillance under the DQST is prompted in part by recommendations from CDER and ORA headquarters and FDA district offices based on their intelligence and reported consumer complaints.

The goal of the DQST compliance program is to protect the public health by minimizing exposure to non-compliant and/or poor-quality drugs. Testing is undertaken on finished dosage forms, APIs, and excipients and the samples chosen are based on risk-based selection criteria and a risk-based model. Due to the globalization of pharmaceutical products increasing consumer risk, the surveilled domestic and international products have expanded under this program to include prescription and OTCs, compounded drugs, drug products with approved an NDA or ANDA as well as unapproved drug products and others. This program, in combination with other quality assurance compliance programs, is an integral part of the Agency’s overall post-marketing surveillance strategy. Fortunately, the majority of drugs FDA independently tests meet their specifications. From 2003 to 2013, FDA tested nearly 4,000 of drug samples. During that decade, FDA laboratories found that 1.1% of the drug products analyzed deviated from acceptable standards.

FDA takes its oversight of the domestic and foreign pharmaceutical program very seriously as any safety deviations in these products could have a significant impact on public health. Companies may wish to proactively perform quality assessments and gain an understanding of their current compliance status through independent third-parties such as qualified consulting firms who offer expertise in pharmaceuticals conducted by persons with a strong background in Agency regulations and safety standards. Once a needs assessment has been conducted, a proactive remediation plan of deficiencies can begin.

More information on FDA’s pharmaceutical surveillance programs can be found on the Agency’s website and we invite you to view EAS-produced on-demand webinars focusing on a variety of GMP tools on the EAS website. Should EAS be of service to your firm either in an assessment of compliance status or to assist with an FDA announced facility inspection, please contact Bryan J. Coleman, Senior Director of Pharmaceuticals and Medical Devices.

Getting Your Medical Device Into the U.S. Market

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If you are a manufacturer whose medical device is either a Class I, or a 510(k) exempt device Class II device, consider yourself and your company lucky that you do not have to try to “thread the needle” of the litigious and arduous process known as 510(k) clearance. Getting a device ready for 510(k) submission is usually time-consuming, costly, and full of challenges.

All 510(k)’s are based on the concept of substantial equivalence (SE) to a legally marketed (predicate) device. If you are the maker of a Class II medical device or an IVD and want to launch it in the U.S. market, you must submit a 510(k) to the FDA. For Class III devices, a premarket approval (PMA) submission is needed.

510(k)’s have unique content and format requirements – they are not identical to a European Technical File – and the FDA’s recent changes to 510(k) requirements make the submission process more rigid than ever.

Class II devices are designed to perform as indicated without harming patients or users, but they require a greater level of safety and effectiveness assurance than do Class I devices. Examples include powered wheelchairs, infusion pumps, surgical drapes, surgical needles, suture material, and acupuncture needles.

Class III medical devices do not have enough information to ensure safety and effectiveness through the general or special controls used for Class I or Class II devices. These higher-risk devices need premarket approval (PMA), which includes a scientific review, to ensure their safety and effectiveness. Examples include replacement heart valves, silicone gel-filled breast implants, and implanted cerebral stimulators.

Here are some practical tips for a 510(k) filing:

  • Establish a “Regulatory plan” as early in the process as possible. The regulatory plan should include a list of all the deliverables required. The plan needs to be owned by all the applicable team members not just the person issuing the plan.
  • Don’t be surprised or disheartened that questions will arise despite your best efforts. The FDA is swamped with 510(k) reviews and any deficiency that they can find in your submission allows them to go to the next submission to keep the commitment that the FDA will review all submissions in a timely manner. “Put yourself in the FDA examiner’s shoes”.
  • Don’t try to blind the FDA examiner with excessive or extraneous information in the hope that they will bypass the information for the sake of time. In my experience, the FDA examiners read every document and every page!

The FDA sends back most 510(k)’s during the first review cycle to request more information – in recent years this has applied to more than 70% of 510(k) submissions!

Also, many medical device companies are compiling and submitting 510(k)’s to the FDA for review without establishing a Quality Management System and without documenting Design Controls and without documenting Risk Management which can bode trouble for the submission as well as FDA inspection time.

You might want to consider using a competent consultant or at least asking an objective party to review the submission for completeness before sending it to the FDA. This will minimize the risk of delay and rejections.

FDA 483 Responses – Missing the Mark?

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In recent months, it appears more companies are having difficulties meeting the requirements of FDA Form 483, List of Observations, response. The inspection situation is very stressful and if it ends with the dreaded “483”, it can be positively overwhelming. However, when the initial reaction is over, it’s time to rally the staff and prepare the corrective and preventative action strategy that will be presented in the response within the allotted time frame. It is also critical to understand what is expected of the response letter.

The 483 is a list of inspectional observations that is the result of what the inspectors viewed while in your facility. It is a legal document from federal agents performing a law enforcement function where the evidence is the collection of documents and data that the agents evaluated at the company. All of the observations should first be reviewed for accuracy. Hopefully, any discrepancies or misunderstandings were discussed during the closing meeting and resolved, but if they were not found until after the inspectors left the facility, they will need to be addressed in the response. The 483 response is also a legal document so the tenor and exact wording used are critical. It must demonstrate that the company understands the issues, has made the necessary corrective and preventative actions, and that there is documented evidence to verify the latter.

Each observation requires a response and that response must describe the associated corrective and preventative actions are taken. It should be thorough and detailed and written to present steps in the order taken. Procedures and related documents prepared and implemented during these actions must also be included. It is not enough to only describe actions, there must be documented evidence of the correction such as photographs, procedures, training records, specific forms, and other types of documentation. Many Warning Letters are issued by the FDA because a company’s response letter did not include evidence of the corrective and preventative actions taken for the FDA to evaluate to determine if the situation was appropriately addressed.

Consider three potential categories of actions to be taken for each observation; immediate, short-term and long-term. Think of this from a medical emergency perspective where initial triage occurs to keep the patient’s condition from getting worse, additional short-term actions are needed to stabilize the patient, and then long-term actions may be needed to deal with any underlying problems. A systematic issue will have to be addressed with preventative measures. It is also important to review the observations collectively, in addition to individual, to determine if other underlying systemic issues exist. These too will have to be addressed with corrective and preventative actions.

Please note that, unlike an FDA Warning Letter, a response to a 483 is not legally required. However, it is strongly recommended that a 483 response be provided to the FDA within 15 business days. Some observations can be appropriately addressed and the actions concluded within this time frame, but others, particularly systematic issues, may require more time. When that is the case, all of the planned corrective and preventative actions should be described in the initial response, immediate and short-term actions should be taken, and completion dates for long-term items provided. It is important that these proposed dates be aggressive, yet reasonable and obtainable. Monthly updates to the FDA stating the progress made on these long-term items, with supportive documented evidence included, should then follow. This strategy may prevent the FDA from escalating enforcement actions and issue a Warning Letter.

Confirmation that the FDA is satisfied with the 483 response will be provided by the issuance of an Establishment Inspection Report (EIR) which states that all of the corrective and preventative actions will be evaluated upon “the next inspection.” The EIR is also a more detailed summary of the inspectional findings and it is wise to use this as an opportunity to further review operations, controlled processes, and the overall quality system. Look at these findings from a systems approach; facilities and equipment, materials, production, packaging and labeling, laboratory controls and, of course, the most important and critical one – the quality incident system. The entirety of the inspection and the inspectional review should also be another piece to the internal audit program, make the experience work to improve compliance and not just an exercise in writing letters to the FDA.

For assistance in understanding FDA 483 findings as well as developing an appropriate response and corrective actions contact EAS.

FDA Food Code 12th Edition – What’s New?

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The FDA Food Code is used as the basis for food safety regulation of more than a million restaurants, retail food stores, institutional and other food operations in the US and around the world. It is updated every two years through a collaborative process with the Conference for Food Protection where all stakeholders have a voice in what is included in the next edition published by FDA. Allen Sayler, Senior Director for Food Consulting Services, in his March column in the EAS-e-News announced the release of the 2017 edition on February 12, 2018.

This article will focus on the 10 major changes in this 12th edition since the first modern risk- and the science-based code was issued by FDA in 1993. Twelve earlier editions had been published by FDA and the U.S. Public Health Service since 1934 that were more retail segment-specific guidance, i.e. food service, food store or food vending.

FDA Food Code only becomes a regulation when its requirements are adopted by local, state, and federal food programs for their segment of this vast industry. The new provisions also become the de facto standard of prudence for many companies, even before their operations are required by the local regulatory authorities to comply with it.

A summary of the 10 major updates in the 2017 edition of the FDA Food Code is provided below. This release also had many less significant changes and numerous editorial and clarification amendments.

Chapter 2 Management and Personnel
2-102

 

 Certified Food Protection Manager

Required, for the first time, that the Person in Charge of the food establishment be a Certified Food Protection Manager. The program that awards this recognition must be accredited, meaning that it has been evaluated and listed by an accrediting agency, as conforming to national standards for organizations that certify individuals.
2-103 Monitoring of Food Temperatures

Added a new duty for the Person in Charge, ensuring employees are routinely monitoring food temperatures in hot and cold holding.
2-201 Salmonella Typhi and nontyphoidal Salmonella distinctions

Expanded on the changes begun in the 2013 Food Code in emphasizing the importance of nontyphoidal Salmonella (NTS), such as S. enterica serotypes, that cause more than one million domestically acquired foodborne illnesses in the United States each year.
2-401 Bandages, Finger Cots or Finger Stalls

Required the use of a single-use glove to cover a bandage, finger cot or finger stall used on the wrist, hand or finger.
2-501 Written Vomit and Diarrhea Clean-Up Procedures

Required that a written plan be provided for cleanup of these bodily fluid discharges by employees or customers. A very good detailed explanation for the plan elements is provided in Food Code’s Public Health Reasons Annex.
Chapter 3 Food
3-401 Changed Cooking Times

Raised the cooking temperature dwell time for foods like comminuted meats requiring a cooking temperature of 68°C (155°F) from 15 seconds to 17 seconds. Lowered the cooking temperature dwell time for foods like poultry requiring a cooking temperature of 74°C (165°F) or above to < 1 second (instantaneous).
3-502 ROP Frozen Fish Labelling

Added criteria for fish that is reduced oxygen packaged at retail to bear a label indicating that it is to be kept frozen until time of use.
Chapter 8 Compliance and Enforcement
8-201 HACCP Plan

When a Hazard Analysis and Critical Control Points plan is required by a jurisdiction for variances including those for specialized processing at retail, more detailed information is required to be submitted for the jurisdictions review and approval.
8-402 Regulatory Training

Added requirement for the Regulatory Authority to ensure that authorized representatives, who inspect food establishments or conduct plan reviews for compliance with Food Code, have access to training and continuing education, as needed, to properly identify violations and apply the Food Code. You will see in this month’s FSMA Perspective that employee training is also a requirement of FSMA and documentation of that training should be kept and provided to FDA upon request during an inspection.
8-404 Utility Interruption Contingency Plan

Allowed the regulatory authority to agree to continue operations during an extended water or electrical outage, if written operational plans have been approved by the regulatory authority.

 

As mentioned with the changes outlined in Section 2-501, the Public Health Reasons in Annex 3 provide excellent plain English descriptions of the science and other details behind the requirements of the changed, as well as the older sections of FDA Food Code. Additional information can be provided by the adopting regulatory authority or by the FDA National Retail Food Team. Questions of FDA on the Food Code may be directed to RetailFoodProtectionTeam@fda.hhs.govor should you have questions which you would like to direct to EAS, contact Allen Sayler at ASayler@easconsultinggroup.com

Medical Device Innovations and the Regulatory Landscape

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I’m amazed as I watch a Health Care System and then a Spectrum commercial to what our future holds with the sophisticated, interactive medical device and technology innovations and how they will enhance the capabilities of diagnosis and treatment. My regulatory mind then kicks in and wonders how these amazing innovations will pose operational and data reliability challenges for both industry and regulators in areas ranging from clinical trials to device design and development, and ultimately to the commercially approved and marketed devices.

For Federal Agencies and other institutions involved in the evaluation, funding, manufacturing, distribution, and clinical use of medical devices, it is clear that the landscape of these activities will be changing in considerable ways. The increase in minimally invasive methods and devices to reduce lengthy recoveries, developments in decentralized care, tissue engineered devices, advances in diagnostic and “smart” products, to the growing sophistication of electronic medical information systems hold for substantially better-informed diagnoses and treatments. Yet, these same developments will generate increased pressure for more effective data capturing systems and methods to handle the data, coupled with concerns related to device accountability, source, supply/availability, and quality.

Regulatory health authorities around the globe are taking steps to be prepared. Are you ready and will you be in compliance when new and upcoming regulations take effect…

Data Acceptance

The FDA issued a final rule, effective Feb. 21, 2019.

Under the new rule, FDA is requiring sponsors and applicants to affirm that clinical investigations outside the United States were conducted in accordance with Good Clinical Practices (GCPs) when the data are submitted for medical device applications.[1] The final rule also amends criteria for investigations conducted within the United States to require applicants and sponsors to state that the investigation complies with FDA regulations for human subject protection, institutional review boards, and investigational device exemptions (IDEs).[2] If an investigation is not conducted in accordance with those regulations, a brief statement of the reason for the noncompliance is required.[3,4]

The US FDA’s new requirements will affect device development strategies, including where to conduct such trials. The necessary patient population in the disease prevalent area of the clinical trial may not have the economic means for network availabilities to fully comply with the use of the sophisticated investigational device product. Education of ex-US trial sites will need to be enhanced, and cost of ensuring trial sites have adequate systems and equipment to effectively run and capture trial data will need to be considered as part of the strategic site selection process without creating bias.

European Union’s (EU) Medical Device Regulation (MDR)

The EU MDR is expected to come into effect in late 2019 or early 2020. This will give national regulators more control and oversight of the medical devices industry. The aim of the new regulation is to ensure that products are effective and safe as well as can be freely and fairly traded throughout the EU. The impact of this regulation can alter the operations of medical device manufacturers most notably on the supply chain and quality management systems of the organizations. It is critical that industry takes steps now to prepare their organizations and start implementing changes.

Data Integrity

Data integrity continues to be a priority and a hot topic. Regulators are focused to detect data integrity, data manipulation, and fraud. They must be able to rely upon the accuracy and completeness of the data and information generated, providing assurances to the products’ safety, identity, strength, purity, and quality which are all dependent on the validity of the data and information obtained.

Conclusion

Regulators are gaining more control and oversight of the medical devices industry. They are taking steps to prepare for the new innovations and enhanced capabilities of diagnosis and treatment with medical devices. It is important for medical device companies to proactively prepare for these changes as their impact could be significant. These include impacts on the cost of implementing changes to organizational prioritization and to internal processes around device accountability/supply, source, availability, and quality. If industry and regulators continue to maintain their role of ensuring compliance, new innovative devices can be made available, safely and effectively for patients, providing for better healthcare outcomes.

[1] US Food & Drug Admin., Human Subject Protection; Acceptance of Data from Clinical Investigations for Medical Devices, 83 Fed. Reg. 7366(Feb. 21, 2018) (hereinafter Medical Device Rule).

[2] See 21 C.F.R. §§ 50, 56, 812.

[3] 21 C.F.R. § 812.27(b)(4)(ii).

[4] Medical Device Rule at 7370.

Clean Label, the Challenges

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So, you decided to have clean labels for your products, now what do you do? You are not alone in your pursuits of this endeavor. A couple of years ago, I was approached by a marketing department when they wanted to make certain claims in their product lines and one of the phrases they used was “we want to say that our labels are clean because our clients want this”, so I asked them, ‘What do you mean by clean?” And of course, having several people in that meeting, I got several different answers! Answers like “no GMO’s”, “Natural”, “Gluten-free”, “No antibiotics”, “No pesticides”, “No Artificial ingredients”, etc. So, the first task at hand was to clarify what the term “clean label” means. At that time, we did not find a definition either from USDA-FSIS or FDA for the term “clean label”, what we found was that the term was probably developed by consumers as an “understandable” claim or answer to ingredients in their food. The Clean Label trend has taken center stage and found its way into many respected scientific meetings. The 2015 Institute of Food Technologist Annual Meeting and Food Expo is just one example of many where the topic of Clean Labels and what that means, was discussed.

When the US-based food retailer, Whole Foods Market, published a list called “Unacceptable Ingredients for Food1” around 2014, they began working with their suppliers on creating products only with natural ingredients as part of their Food Ingredient Quality Standards. Around the same time, Panera Bread published their “No No List2” of ingredients, such as preservatives, sweeteners, flavors, and colors, all from artificial sources, that were no longer allowed in their products. The trend was not just U.S.-focused as many International companies were also working on making their labels more transparent to help consumers make better decisions.

So, what does “clean label” mean? Many definitions exist, and all include the fact that terms such as “no artificial ingredients” and/or “natural” are included on labels as consumers expect transparency by using ingredient names that people can recognize. One of my favorite definitions of a “clean label” came from my wife (not biased!) who said that a clean label is one where she understands ingredients in her food without having to ask me and that the ingredients do not come from artificial sources.

This transparency is a great and noble cause to pursue but what are the challenges? In my opinion, the first challenge facing the technical and scientific community is that functionality in many cases drives the choice of almost all ingredients: things like water retention (phosphates), color additives (FD&C Red No. 3 and 40), color development/enhancement (sodium nitrate in processed meats) and flavor enhancement agents (MSG or Monosodium Glutamate not naturally occurring). Some ingredients already have a natural alternative, like the use of celery powder and sea salt as a source of naturally occurring nitrate-nitrite but we are still working on alternatives for others, creating challenges to R&D scientists and chefs all over the country.

This R&D also creates the second challenge in my opinion: cost. Many of these “clean” ingredients are expensive either because of the amount of these “clean” ingredients required or the increase in demand just in the last couple of years. Before a company decides to reformulate, understand your audience and your clients to ascertain whether they are demanding this change or not. I was surprised when the company asked their marketing group to investigate whether the demand for clean ingredients was universal, that only a small percentage of clients were demanding a change to clean labels. Based on that research they decided to invest time in creating a brand-new line of products to fulfill this need instead of reformulating all products.

In my opinion, some of the questions you need to ask before you start changing formulas are:

  • Are all my clients and/or target markets demanding a clean label?
  • Are they willing to pay for this change?
  • Can I afford the change?
  • Do we change our formula or do we create a new line of products?

Depending on your answers, you will be able to make an informed decision for the future of your company.

Note: This article presents the point of view of the author and does not represent any legal advice.

References

  1. Whole Foods “Unacceptable Ingredients for Food”
  2. Panera Bread “No No List”

Homeopathy – What Does the Future Hold?

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It’s been clear for several years that the FDA, as well as the Federal Trade Commission (FTC), are turning up the heat on homeopathic drug products. It culminated in December 2017 when the FDA published a draft guidance document for both FDA staff and industry regarding their new approach to regulating “Drug Products Labeled as Homeopathic”. This followed on the heels of FTC’s “Enforcement Policy Statement Regarding Marketing Claims for Over-the-Counter Homeopathic Drugs” published in 2016.

The practice of homeopathy has been around for more than 200 years and has its share of both critics and adherents. Homeopathy is a form of alternative medicine based on the concept that a disease can be treated with minute quantities of natural substances that would, if given in larger amounts to a healthy person, produce symptoms of the same disease.

Prior to this most recent regulatory action, the FDA regulated homeopathic medicines as drugs under the Federal Food Drug and Cosmetic Act but did not otherwise evaluate their safety and efficacy as long as they were marketed for self-limiting conditions and contained active ingredients listed in the Homeopathic Pharmacopeia of the United States. The enforcement policy was described in a Compliance Policy Guide (“Conditions Under Which Homeopathic Drugs May be Marketed”) that was issued in 1988.

As the homeopathic industry grew, the Agency re-evaluated its position and announced in 2015 that it was going to evaluate the regulatory structure for these products. It hosted a public meeting that spring during which interested parties (manufacturers, health care professionals, industry associations, etc.) could provide input and make suggestions as to whether the current framework was appropriate for ensuring the safe use of these products. As a result of the meeting and FDA’s own evaluation, it determined that a new guidance document, applying a “risk-based” approach to enforcement, would better serve public health and be consistent with the Agency’s general approach to products marketed without FDA approval.

Because there are currently no homeopathic products approved by the FDA, the guidance document, when finalized, would serve notice that any product labeled as homeopathic could potentially be subject to enforcement action. However, the FDA recognizes that some categories of products pose a greater risk to public health and so provided a list that would receive prioritized enforcement. These include:

  • Products with reported safety concerns
  • Products that contain or purport to contain ingredients associated with potentially significant safety concerns
  • Products for routes of administration other than oral or topical
  • Products intended to be used for the treatment of serious and/or life-threatening diseases and conditions
  • Products for vulnerable populations
  • Products deemed to be adulterated under the Food, Drug and Cosmetic Act

As noted earlier, in addition to this increased FDA oversight, the FTC (which monitors marketing and promotional claims) is taking a more proactive approach to homeopathic drugs. In the aforementioned policy statement, it indicated that OTC homeopathic drugs would be held to the same standard as other products with regard to claims. In other words, companies either needed to have competent and reliable scientific evidence to back up the claims OR, alternatively, they could revise their labeling to include disclaimers communicating that “there is no scientific evidence that this product works and that its uses are based on theories of homeopathy from the 1700s that are not accepted by most modern medical experts.” No longer would it be acceptable to rely on statements that the “FDA has not evaluated the product” or that the treatment relied on “homeopathic principles”.

These actions by the FDA and FTC are not encouraging to the homeopathic industry. How strictly this new approach will be enforced is unknown, especially in the current political climate of decreased regulation. However, it’s a safe assumption that any homeopathic product that presents a safety risk or makes egregiously deceptive claims, will likely come under scrutiny and could land the offending company in proverbial “hot water.”

Have a Cup of Coffee and Pray – It’s the 20th Anniversary of the Seafood HACCP Rule

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HACCP, of course, stands for Hazard Analysis Critical Control Point, is a highly effective preventive control system for foods and other commodities. “Have a cup of coffee and pray” was how one skeptical USDA union official described HACCP implementation in meat and poultry processing plants when it was implemented in the early 2000’s. It is an example of some of the reservations public health officials had as early as 1980. FDA implemented this systematic control system in seafood effective December 1997. Although controversial its implementation proved to be a tremendous success for the agency and public health in general.

First, let me provide a little history. In the early 1980’s there was a developing trend towards exercise and healthy eating. A nutritionist named Anne Fletcher published a highly popular book about the nutritional benefits from eating seafood entitled Eat Fish, Live Better. This book received a tremendous amount of attention in the media that spurred the consumption of seafood as part of a healthy lifestyle. However, the seafood industry at the time had some systemic quality control problems that allowed significant amounts of low-quality seafood on the market. Most of these quality problems were hygienic in nature and did not pose a food safety problem. However, it did cause concern in the media about seafood safety and the public began to believe that seafood was good nutritionally but not always safe.

Congress at the time also became concerned about seafood safety and offered various legislative bills for so-called mandatory inspection of seafood. Congress also provided money for a Model Seafood Surveillance Project whose mission was to determine what governmental regulations were needed to address these issues. NOAA Fisheries conducted the project and dozens of workshops with industry to garner feedback about what would address the issue of safety and would work best for them. The conclusion of that report was that the implementation of mandatory HACCP was the best way forward. Circa 1990 President H.W. Bush ordered FDA and NOAA Fisheries’ Seafood Inspection Program to work together on a voluntary joint program to implement HACCP principles into the seafood industry and under President Bill Clinton, then FDA Commissioner Kessler decided that FDA would develop its own mandatory program for Seafood HACCP.

The resulting Seafood HACCP rule can be best understood and implemented by referencing the FDA drafted complex guidance document called the Fish and Fishery Products Hazard Guide (FFPHG). It is used worldwide as the, most authoritative, comprehensive guide to the science behind HACCP and FDA policies related to seafood.

While seafood HACCP regulations have been in place for 20 years, there is always work to do and vigilance to keep with regards to the safety of our food sources as the volume of seafood imported to the United States continues to increase. In 2009, 80 percent of the seafood in the U.S. food supply was imported, and by 2015, more than 90 percent was imported. A quick review of FDA warning letters at any point in time demonstrates this challenge, with as of this writing, six out of ten of the most recent FDA warning letters pertaining to seafood HACCP. Challenges such as implementing and verifying that seafood is processed, held and transported insanitary conditions; that regular inspection records verify their safe handling, both before they reach US shores and when they are a domestically distributed are areas where FDA inspectors are working diligently.

Over the years the guidance and FDA policy thinking was refined and the regulation became a tremendous success. Seafood safety and quality improved, scientific thinking was imbued into the seafood industry through the FFPHG which promoted the health of consumers, consumers were less worried about safety issues and seafood HACCP became a template for the Food Safety Modernization Act of 2010 that would apply preventive control principles to the manufacturing of all food commodities. That’s quite an accomplishment. So let’s have a cup of coffee and praise the FDA for their fine work in improving food safety standards for seafood.

FDA’S Policy on Medical Foods

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“Medical food” is a commonly misunderstood term as it is used on FDA regulated products. Many manufacturers want to market their products as medical foods because medical foods are exempt from the disease statement limitations for health and structure/function claims and are allowed to name the diseased population for whom they are designed. The following paragraphs provide details on FDA’s approach to medical foods, but the policy can be summarized as: a medical food is intended for people who have a disease or condition that results in a distinctive nutritional need which cannot be met by a diet of regular food but is met by the medical food. The disease or condition must be identified, the distinctive nutritional need must be substantiated by data, and it must be demonstrated that the product would meet the identified nutritional need.

Prior to 1972, medical foods were primarily formulas for managing patients with inherited metabolic diseases. They were mainly orphan products for limited populations. They were considered drugs to ensure their use under medical supervision. However, in 1972 the FDA reclassified these products from drugs to foods for special dietary use to enhance their development and availability. In the intervening years, a wide variety of products categorized as medical foods have been developed. Currently, marketed medical foods with a wide variety of claims are used extensively as a life support modality in the management of the critically ill and elderly. They are required to conform only to those regulations dealing with general food safety and labeling to be distributed in the United States.

The 1988 Orphan Drug Act (21 U.S.C. 360ee(b)(3)) provides financial incentives (such as drug application fee exemptions, and market exclusivity) to promote the development of “orphan drugs” for treating rare diseases and conditions. Medical foods were included in the Orphan Drug Act to include dietary therapies, along with pharmaceuticals, as eligible for financial incentives for developing orphan drugs. Medical food was defined within the context of new drug development, not for regulating the use of such products. The Orphan Drug Act did not amend the FD&C Act to add medical foods as a regulatory category.

The Orphan Drug Act definition of medical food is:

A food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.

There are presently no FDA regulations specific to medical foods other than the exemption provisions in the nutrition labeling regulation. The following criteria that clarify the statutory definition of a medical food can be found in FDA’s regulations at 21 CFR 101.9(j)(8). A medical food is exempt from the nutrition labeling requirements of 21 CFR 101.9 only if:

  1. It is a specially formulated and processed product (as opposed to a naturally occurring foodstuff used in its natural state) for the partial or exclusive feeding of a patient by means of oral intake or enteral feeding by tube, meaning a tube or catheter that delivers nutrients beyond the oral cavity directly into the stomach or small intestine;
  2. It is intended for the dietary management of a patient who, because of therapeutic or chronic medical needs, has limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone;
  3. It provides nutritional support specifically modified for the management of the unique nutrient needs that result from the specific disease or condition, as determined by medical evaluation;
  4. It is intended to be used under medical supervision; and
  5. It is intended only for a patient receiving active and ongoing medical supervision wherein the patient requires medical care on a recurring basis for, among other things, instructions on the use of the medical food.

FDA published in 1996 an Advanced Notice of Proposed Rulemaking (ANPR) in which the agency discussed its interpretation of the Orphan Drug Act definition of medical food. (https://www.gpo.gov/fdsys/pkg/FR-1996-11-29/pdf/96-30441.pdf) While FDA later withdrew this ANPR due to lack of resources to devote to the subject of medical foods, the agency stated that it still retained the positions described in the document. A subsequent guidance document on medical foods provided advice consistent with positions in the ANPR. (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm054048.htm)

FDA considers the statutory definition of medical foods to narrowly constrain the types of products that fit within the category. Outside of medical foods that have been developed for dietary management of rare diseases, FDA has considered most products marketed as medical foods, not to meet the definition of a medical food. The types of products that have been the target of FDA medical food Warning Letters include products intended for the dietary management of allergies and asthma, lactose intolerance, psoriasis, constipation, Irritable Bowel Syndrome, Crohn’s disease, colitis, arthritis, failure-to-thrive, injury/trauma, pre/post surgery, and prenatal vitamins. The FDA guidance document specifically states that pregnancy and diabetes are not diseases or conditions for which there is a distinctive nutritional need that could only be met by a medical food.

Pharma’s Problems with Data Integrity

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Data Integrity needs to be taken seriously in the pharmaceutical industry today and always! The FDA has issued many Warning Letters and Import Alerts to dosage form and Active Pharmaceutical Ingredient (API) manufacturers in the past several years. Manufacturers need to understand that once FDA finds some of your data to be unreliable, then they consider all your data unreliable. Many companies continue to use paper records [21 CFR Part 11 does not require you to use electronic records] and this is acceptable.

Problems have been found recently with the lack of compliance with chromatographic data acquisition systems used in quality control laboratories to test the potency of drugs and API. These data systems such as LIMS and Empower must be validated to comply with the regulations in 21 CFR Part 11. Electronic audit trails include those that track creation, modification, or deletion of data (such as processing parameters and results), those that track actions at the record or system level, such as attempts to access the system or rename or delete a file.

The Data Integrity regulations have been official since 1997. These new regulations have enabled a new industry to sprout, 21 CFR Part 11 compliant hardware and software. In addition to the hardware and software companies, consulting companies specifically focused on Data Integrity Compliance have also arisen. Please use caution as these electronic data systems must be validated at your site, using your systems, to truly claim that these systems are validated. Do not just take the vendor’s word for it that their data systems are compliant with this new regulation.

FDA expects that data to be reliable and accurate. CGMP regulations and guidance allow for flexible and risk-based strategies to prevent and detect data integrity issues. Firms should implement meaningful and effective strategies to manage their data integrity risks. This should be based upon their process understanding and knowledge management of technologies and business models. In recent years, FDA has increasingly observed CGMP violations involving data integrity during CGMP inspections. This is troubling because ensuring data integrity is an important component of Industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s ability to protect the public health. Not to mention compliance with FDA regulations is the most sound business model for success.

The following statement is taken from a Warning Letter issued to a foreign manufacturer in 2016:

Our inspection revealed that your firm selectively omitted CGMP records directly related to the testing and manufacturing of your products. You are responsible for the accuracy and integrity of the data generated by your firm. A firm must maintain all raw data generated during each testing and manufacturing operation, including graphs, charts, and spectra from laboratory instrumentation. You must properly identify these records to demonstrate that each released batch was manufactured in accordance with validated parameters, was tested appropriately, and met release specifications. Your firm’s executive management is responsible for ensuring the quality and safety of your products. Implementing adequate controls and systems to prevent omission and manipulation of laboratory data is at the foundation of fulfilling this critical responsibility.

FDA’s Guidance for Industry on Data Integrity and Compliance With CGMP is available at http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/ guidances/ucm495891.pdf

This guidance contains a wealth of information, which will help companies understand the definitions and requirements regarding data integrity. FDA’s Introduction to this guidance is included as follows: The purpose of this guidance is to clarify the role of data integrity in current good manufacturing practice (CGMP) for drugs, as required in 21 CFR parts 210, 211. This guidance provides the Agency’s current thinking on the creation and handling of data in accordance with CGMP requirements. These data integrity regulations are included in 21 CFR Part: 11 Electronic Records; Electronic Signatures. This URL includes the 21 CFR Part 11 regulations: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11

As always, consultants with expertise in data integrity, such as EAS Consulting Group, can provide the independent third-party validation that your company needs to ensure processes and procedures are accurately testing the data in question and that data is yielding meaningful results needed to verify integrity and validation. As mentioned, once FDA finds some data to be unreliable it considers all data to be unreliable. Full compliance with 21 CFR 11 will enable FDA to have trust that your data results and ultimately products are safe to market in the US, saving time and money.

Our Year in Review

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As 2017 draws to a close, it is appropriate to reflect on a year full of change, important milestones and growth not only at FDA but also here at EAS Consulting Group. Both organizations saw new staffing and new initiatives. With the inauguration of President Trump, FDA saw a changing political dynamic with new enforcement policies, and guidance documents; and on the EAS front, new staffing, partnerships and initiatives were aimed at helping the industry conduct efficient, safe and compliant business in order to meet FDA requirements.

Here are some highlights from 2017 which we think best demonstrate the commitment of both FDA and EAS to better the greater good.

On the FDA front:

Most significantly for FDA, Scott Gottlieb was confirmed as the new Commissioner. Under his guidance a number of initiatives are underway in all regulated industries, with some specific highlights in pharma, medical device and food mentioned here.

In the area of pharmaceuticals, the compliance date for Drug Master File electronic submissions was extended until May 5, 2018, giving a bit more time for the industry to get a handle on this complicated process. EAS, which has long assisted pharma manufacturers in technical review of stability data and assembling applications and reports added the additional service of electronic filing preparation and submission over two years ago in anticipation of FDA’s move to this requirement. Those firms who have not already updated their processes to e-CTDs, as they are commonly called, should be fully engaged in doing so now.

The Class II Medical Device industry had a reprieve in July when FDA published a sizable list of class II medical device products that no longer require premarket notification under section 510(k) of the FD&C Act (21 U.S.C. 360(k)), to provide reasonable assurance of safety and effectiveness, subject to certain limitations. Medical device 510(k) filings are a laborious process with many confusing elements. Readers may wish to refer to our August 2017 EAS-e-News issue of the month article, where Independent Consultant Joe Ouellette, discussed some ways to simplify the process. If your company requires 510(k) filling assistance, EAS has many medical device experts who can help with these requirements.

The U.S. Agent verification for medical device facilities process saw a change in October whereby U.S. Agents must now confirm with FDA their consent to act in that role. EAS provides U.S. agent services to countless foreign clients. This is not only an FDA requirement, EAS prides itself on providing comprehensive services in this area with open and free flowing communication between the client and FDA as well as answering questions on various FDA matters which can be confusing. In EAS, foreign firms have a dedicated liaison with the agency.

On the Food Safety Modernization Act front, new enforcement requirement deadlines continued to move forward. May 30 was the deadline for food importers to notify FDA whether their products are subject to FSVP regulations. Our Independent Advisor for FSMA, Charles Breen, writes a monthly column on the latest requirements for EAS-e-News, called FSMA Perspective and we have offered numerous webinars on the various requirements, free replaysof which can be found on our website. You may also be interested in our handy digital FSMA Pocket Guide, downloadable and searchable for easy reference on the go.

A significant change for food manufacturers was a 1.5-year extension of compliance dates for new requirements for updated nutrition information on food labels, including dietary supplements. Public comments were requested through November 1, 2017 on various considerations such as the definition of a single-serving container; a dual-column labeling for certain containers; reference amounts customarily consumed (RACCs); and amending the label serving size for breath mints. Even with this extension, EAS saw record numbers at our recently held Food Labeling Compliance Seminar and continues to provide in-house trainings on the subject as well – an indication that the industry at-large is preparing for compliance in advance of FDA’s deadlines.

On the EAS front:

EAS has seen fantastic growth in the past year. With new regulations and requirements set forth by the agency, novel technologies and products requiring the design and review of stability studies, toxicology, data review and statistical analysis prior to highly technical application submissions, FDA regulated industries have sought our support in meeting these requirements. Through outsourcing expertise to firms such as ours, companies are able to enhance their technical capabilities in a cost effective manner.

To meet these demands, EAS gained two new director level positions, welcoming Allen Sayler as Senior Director, Food and Cosmetics Consulting Services in January. His addition to EAS senior management greatly increased our competencies into the dairy industries. Tara Lin Couch, Ph.D., became Senior Director Dietary Supplement and Tobacco Services in August. Tara’s expertise in the dietary supplement industry has been well known to our clients since 2012 when she first joined EAS as an Independent Consultant. She was appointed to the position of Independent Advisor for Dietary Supplements in 2015. Timothy Stewart, Ph.D. accepted the role of Independent Advisor for Dietary Supplements in October. EAS also added 33 new Independent Consultants, accomplished experts in their fields who have hit the ground running in support of our clients and training initiatives.

We also expanded our partnerships through a relationship with Almater Food Technologists based in Italy. This unique collaboration will enhance the ability of EAS clients who seek assistance in exporting foods into the EU as well as Almater’s clients who seek additional assistance with FDA compliance.

Our Product Development and Labeling Strategic Services initiative, started in 2016, saw huge growth as companies continue to seek advice on how to position their products and guidance on the proper use of various claims such as “healthy”, “natural” and GMO labeling. The success in this area has led to the creation of additional specialized teams of independent consultants who can address client needs requiring multiple areas of expertise.

EAS greatly increased our training capabilities in 2017. Our Food Labeling Compliance seminar was awarded 16 CEUs by the prestigious Commission on Dietetic Registration, lending further credence to the quality of our long running program, and providing an additional service to those participants who seek continuing education credits. We are proud that a number of our Independent Consultants are Lead Instructors for Preventive Controls for Human Foods (PCHF) under the Illinois Institute of Food Technology’s Food Safety Preventive Controls Alliance, and for the Foreign Supplier Verification Program (FSVP) under the International Food Protection Training Institute. EAS also became a training center for the Safe Quality Foods (SQF) 8.0 and Quality courses under the Safe Quality Foods Institute. Finally, Allen Sayler’s popular Dairy Processing 101 three-day seminar has become a new fixture in the EAS training center.

Finally, EAS was honored to be invited presenters at over 30 trade organization conferences and tradeshows and webinars for outside organizations. From the Institute of Food Technologists (IFT), Food Drug Law Institute (FDLI) Consumer Healthcare Products Association (CHPA), National Customs Brokers and Forwarders Association of American (NCBFAA) and the Safe Quality Foods (SQF) our Independent Consultants and home office staff are well recognized and sought-after experts in their areas.

As we look towards 2018 we are anticipating more movement by FDA in areas such as tobacco as the agency seeks input on its new initiative of pursuing lower nicotine levels in cigarettes to non-addictive levels and create more predictability in tobacco regulation. EAS is one of very few consulting firms to offer comprehensive services to the tobacco industry and we take an active role in the trade organization the Tobacco Manufacturers Association.

As always, EAS stands at the forefront of tracking industry regulations and applying those requirements in a practical and meaningful way for clients. We take great pride in our expertise and ability to provide quality regulatory assistance. We welcome your inquiries as to how EAS may help your business and above all wish you a happy and prosperous 2018.

A Look at the Regulation of OTC Sunscreen Formulations

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The process of developing and testing a sunscreen is not unusually difficult but it does require close attention to the regulations and coordination with the testing laboratory preparing the efficacy data.

Sunscreens may be part of a cosmetic line and those that are intended to provide protection from incidental sun exposure during the normal day’s activities are often called “cosmetic sunscreens”. On the other hand, sunscreens intended to provide protection from prolonged sun exposure activities such as beach, pool, or other activities where sun exposure is high and resistance to water or perspiration is required. These products are often called “active or sport” formulations. The formulation requirements for each class are slightly different but the underlying regulations for the products are the same.

In the United States, sunscreens and several other categories of functional products are regulated under the over-the-counter (OTC) drug regulations of the Food and Drug Administration (21 CFR 352). These regulations define the allowable active ingredients (termed UV filters) and their maximum use concentrations, the performance testing required to establish the efficacy of the product (SPF, Broad Spectrum coverage, and water resistance), and labeling of the product.

An important concept of the OTC program is that the active ingredients used in the formulation will be considered safe provided that the regulations are followed. Therefore, the individual new formulation does not require approval from FDA. The specific OTC drug regulations for sunscreens are unique to the United States, but many of the same principles apply in many markets. In the European Union, sunscreens are regulated as cosmetics (for labeling) but certain restrictions for active ingredients and testing apply.

In all major markets, the active ingredients that can be used as UV filters are prescribed by positive lists (that is, only ingredients on the specific list for that market may be used). The maximum concentration of each active ingredient is also indicated. These lists for both specific ingredients and maximum concentrations are not the same across markets. Thus, a product prepared for one market may well not be acceptable in another. For example, the United States has a shorter list of approved UV filters than does the EU and so many EU products are excluded from the U.S. market.

A functional sunscreen formulation is not simply the sum of its active ingredients. If it were, efficacy testing would be rather easy. The remaining ingredients, termed inactive ingredients under the regulation, are essential not only for the aesthetics of the product but for its efficacy as well. To function effectively, the formulation must hold the UV filters in a film on the surface of the skin. The film holds the UV filters to form a “tortuous path” through which the UV light must pass. The filters scatter and absorb the UV light attenuating exposure to the skin below. Since the surface of the skin is not flat, the formulation must form a film that can cover the skin peaks and valley to block the UV light.

While the formation of a surface film is required for function, it can impact product esthetics. Cosmetic sunscreens, such as facial moisturizers, are intended for incidental UV exposure with limited water or perspiration exposure. These products may be successful with less robust film former. Active or sport formulation require considerable water resistance (once they have dried on the skin) and so need more robust, less water-soluble film formers.

In summary, to ensure regulatory compliance of OTC sunscreen formulations, it’s important to closely follow the regulatory and testing requirements.

U.S. Dairy Industry Challenge – How Many Food Safety Plans Are Enough?

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The U.S. dairy processing industry is facing a significant challenge as it moves toward compliance with the FDA Food Safety Modernization Act (FSMA). This is best captured by a conversation I had with a corporate quality assurance vice president about six months ago. When asked how many written food safety programs each of the dairy plants in his company had, the reply was, “Because of the current regulations, private certification systems, customer expectations and our own corporate food safety requirements, the number ranges between three and five per plant.

I asked how they could manage this number of different food safety programs, which one(s) the plant employees were trained on and how they kept the records required for each written food safety program separated and organized. While he may have had a solution, he did not provide an answer to my question. The challenge is exactly that; with so many demands on dairy plants today to operate in a multi-jurisdictional government world, a multiple customer world and competing, private food safety standards, can one written food safety program meet the requirements for all these different parties?

For many U.S. dairy processing plants, because of industry consolidation, their compliance enforcement deadline for the FSMA “Preventive Controls for Human Foods (PCHF)” regulation was September 2016. The regulation mandates a written food safety program that requires a risk-based hazard analysis incorporating “preventive controls” and development of a supply chain management program. Also, this regulation mandates radiological hazards be considered. The preventive controls program is to be supported by compliance with updated Good Manufacturing Practices (GMPs) found in 21 CFR 117, Subpart B. We will call this “Written Food Safety Plan #1”.

Starting in 2008, many larger dairy companies rebuilt their written food safety programs to comply with the requirements found in one of the Global Food Safety Initiative’s (GFSI’s) recognized third-party food safety certification schemes such as Safe Quality Foods (SQF), the British Retail Consortium (BRC), FSSC 22000 and the International Featured Standard (IFS). While the four GFSI schemes have differences, they all require a written food safety program that utilizes prerequisite programs to support the written HACCP Plan. The hazard analysis part of the HACCP Plan is supposed to incorporate “risk” into the decision-making process but does not require any recognition of potential radiological hazards. The GFSI schemes utilize specific prerequisite programs instead of GMPs to receive their certification. We can designate this as “Written Food Safety Plan #2”.

In May 2017, the U.S.-based National Conference on Interstate Milk Shipments (NCIMS) adopted the most significant changes for Grade “A” dairy plants since the early 1990s. These changes are likely to be accepted by the FDA in October 2017 and enforced in all “Grade A” dairy plants by October 2018. The new requirements will require a FSMA “Preventive Controls-like” written food safety program that will be evaluated by trained FDA Regional Milk Specialists once every three years, in addition to the routine GMP-like state inspections required once every three months. These NCIMS changes are similar, but not the same as required in the FSMA Preventive Controls regulation, with the FDA GMP requirements being somewhat superseded by the NCIMS Pasteurized Milk Ordinance (PMO) dairy plant operational requirements. In addition, the Preventive Control supply chain management requirements were modified to recognize the NCIMS strict requirements for utilizing only raw milk from Grade “A” licensed or permitted dairy farms and dairy ingredients from Grade “A” dairy plants. We recognize this as “Written Food Safety Plan #3”.

Finally, many large dairy companies have mandated policies and procedures on the content and details for a dairy plant’s written food safety plan. These mandated policies and procedures are “enforced” via corporate-based or private auditing companies hired to conduct plant-by-plant assessments. We can call this “Written Food Safety Plan #4”.

The problems related to multiple and possibly competing written food safety programs in dairy plants are significant. First, most dairy plants are challenged, like any food processing plant, with managing one written food safety plan. So how does a plant maintain and implement multiple written food safety programs? Second, how does plant management decide on the instructions and training for the plant staff that are responsible for delivering a safe finished product, based on multiple written food safety plans? Third, most plants are resource-challenged to support one written food safety plan, so where do the resources come from to maintain, implement and train staff on multiple written food safety plans?

A “revolutionary” process is required for a dairy plant with up to four different food safety programs to consolidate into one which contains the key requirements in one written food safety plan. This consolidated plan needs to use hybridization techniques to achieve a “Best in Class” food safety program. Such hybridization in nature many times produces much stronger off-spring with unique and new abilities to meet the challenges of the real world. This is the expectation for the “hybridized”, consolidated written food safety plan that will replace the multiples.

In conclusion, dairy plants need to conduct a hybridization exercise to move toward one “Best in Class” written food safety program that meets or exceeds government, private certification, customer and internal corporate requirements.

With more than 150 independent consultants, EAS has the expertise to assist any dairy plant or company in developing a “Best in Class” hybridized written food safety program. For more information, please contact Allen Sayler, EAS Senior Director of Food and Cosmetic Consulting Services at 571-447-5509 or via email at asayler@easconsultinggroup.com.

Tips for Auditing a Contract Laboratory

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Contract laboratories provide an extremely valuable and necessary service to the dietary supplement industry. The own-label distributor or manufacturer rarely has an in-house laboratory equipped with the appropriate scientific expertise to conduct all the testing required in 21 CFR 111, Current Good Manufacturing Practices (cGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements.However, a contract laboratory must be thoroughly scrutinized by the own-label distributor or manufacturer to ensure the laboratory complies with the applicable subparts of 21 CFR 111.

All personnel must possess the education, training, or experience needed to perform their job function in accordance with 21 CFR 111.12(c). Responsibilities and activities for each job function should be described in a formal job description. A comparison of the job description to on-the-job training provided in a personal training record as well as a resume or biography of several selected individuals should be examined during the audit to verify compliance with the regulatory requirements, but also ensure the laboratory has the scientific expertise to competently perform the desired tests.

The laboratory facility used to perform testing must be adequate per 21 CFR 111.310 and in accordance with 21 CFR 111.27, all equipment must be of appropriate design, construction, and workmanship to enable them to be suitable for their intended use. The latter is generally accomplished using an equipment qualification program. Documentation supporting the qualification of several different types of equipment should be reviewed during the audit. Part of the review must include an assessment of any software or electronic operations being performed by the instrumentation.

All electronic equipment and records must comply with the requirements dictated in 21 CFR 11, Electronic Records, Electronic Signatures. Equipment must then be calibrated and maintained at a frequency dictated by the manufacturer to maintain accuracy and precision and these activities must be documented in equipment log books as governed by 21 CFR 111.35(b)(3).

All laboratory controlled processes, including written procedures for test methods, must be developed and implemented in the laboratory as required by 21 CFR 111.325. There must be evidence that these test methods are being conducted, as written, by laboratory personnel and that this is documented at the time of performance. The documentation must be thorough and detailed and include the performance of each step of the method. Test methods employed must be scientifically valid as required by 21 CFR 111.75(h)(1) and 111.320(b).

The FDA described a scientifically valid test method as one that is accurate, precise, specific for its intended purpose, and consistently does what it is intended to do (rugged). Documentation that a method meets these criteria is accomplished from method validation studies for the sample matrix via experimentation, peer-reviewed literature, or compendial sources. Several examples of such documentation should be reviewed by the auditor.

Other critical laboratory controlled processes to examine during a contract laboratory audit include those for out of specification (OOS) investigations, deviations, and corrective and preventative actions. These situations are inevitable and a strong quality system must be in place for handling them.

There are many important aspects to choosing a contract laboratory, from assessing testing and record-keeping to confirming it is equipped and suitable for its intended use. A pre-audit of a contract laboratory helps to ensure that their procedures match those required by FDA as well as your own internal requirements. This up-front work will go a long way towards finding the right partnership to enable distributors and manufacturers to market safe products.

Changes in What Constitutes ‘Dietary Fiber’ for Nutrition Facts Labeling May be in the Works

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One of the more controversial aspects of the FDA’s final rule on revising the Nutrition Facts Panel (NFP), 81 Fed. Reg. 33742(May 27, 2016), changes the definition of “Dietary Fiber” as it is disclosed on the NFP.

The new rule requires that only certain naturally occurring dietary fibers such as those found in fruits, vegetables and whole grains, and added isolated or synthetic fibers that FDA has determined have a physiological effect that is beneficial to human health, can be declared on the NFP under “Dietary Fiber.” Previously, fibers in foods could be labeled as dietary fiber without necessarily providing evidence of beneficial physiological effects.

Under the final NFP rule, a fiber ingredient that is “intrinsic and intact in plants” automatically meets FDA’s new dietary fiber definition. In addition to fiber that is naturally occurring in foods, the final regulation identifies seven isolated or synthetic non-digestible carbohydrates that, when added to foods, can be declared as “Dietary Fiber.” They are: [beta]-glucan soluble fiber (as described in 21 CFR 101.81(c)(2)(ii)(A)), psyllium husk (as described in 21 CFR 101.81(c)(2)(ii)(A)(6)), cellulose, guar gum, pectin, locust bean gum, and hydroxypropylmethylcellulose.

But other fibers that are “isolated” or “synthetic,” must gain FDA approval and show they have a beneficial physiological effect before they can be counted as “Dietary Fiber” on the NFP. Under the final rule, food manufacturers can submit petitions to FDA for approval of additional sources of “Dietary Fiber” with physiological benefits and many have done so already.

FDA reacted by publishing a request for scientific data, information and comments to help it determine whether certain fibers should be added to the definition of “dietary fiber” published as part of the NFP final rule.

The request for information, along with an accompanying draft guidance, is intended to help industry understand how FDA reviews the scientific evidence to determine whether other fibers beyond the seven identified in the final rule should be added to the regulations. It also provided an opportunity to add to or comment on FDA’s review of the science with respect to whether any of the 26 additional specific types of fiber provide a physiological effect that is beneficial to human health and thus should be included in the fiber definition. The comment period closed on February 13, 2017.

Some segments of the food industry remained unsatisfied. On April 7, 2017, the American Bakers Association (ABA) filed a petition urging the agency to revoke its new definition of “Dietary Fiber” for Nutrition Facts labeling purposes. Whether the ABA’s request will receive serious consideration remains to be seen.

On June 13, 2017, FDA’s Office of Nutrition and Food Labeling announced that it intends to extend the compliance date for the new Nutrition Facts rules. ABA praised the move. But how long the compliance date will be extended and whether FDA also will reconsider certain aspects of the regulation are unknown. FDA Commissioner Scott Gottlieb stated before a Senate Appropriations Sub-Committee hearing on June 20, 2017, “We are not reopening the regulation…We are just using this time to develop additional guidance documents.”

Whether industry dissatisfaction with FDA’s final regulation on the disclosure requirements for “Dietary Fiber” on the Nutrition Facts label will lead to a wholesale change in the agency’s approach, or merely the addition of a few more substances to its list qualifying as having beneficial physiological effects, remains to be seen. But some changes can be expected.

Process Labeling – Pathway to Transparency?

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A thirty-year old federal court opinion that is well known to students of food and drug law holds that in the absence of a detailed, Congressionally mandated definition, courts and regulators should follow the common understanding of “food” as an article that delivers “taste, aroma and nutrition.” In the 21st century, however, food not only nourishes and satisfies, it also frequently makes a statement — about how it was made, where it came from and how the earth and its inhabitants were treated along the way.

Foods with these sorts of claims – called “Process Labeling” — are everywhere. Even on a casual trip to the supermarket, it’s hard to miss the increasing use of labels claiming that a food is “certified organic,” “shade-grown,” “free-range,” or “rain forest certified,” to name but a few. Process labeling is oftentimes also about what was notdone to a food. For example, “Non-GMO” indicates that the food used no ingredients made from genetically modified organisms, or “GMOs,” shorthand for the agricultural bioengineering methods that have helped farmers grow corn, soybeans and other cash crops.

Consumer Appeal

Food marketers today, as one of them recently told me, need to appeal to consumers’ desire to know about the “genealogy” of a food. Of course, this interest is relatively new but growing exponentially and to a very real extent can be attributed to the fact that food in the United States is by and large safe, plentiful and relatively inexpensive. Two authors who have studied communication in modern agriculture explained the phenomenon this way:

As top concerns for consumers are already largely being met, there is a freedom that was not historically available to delve deeper into food issues, to ponder how food was grown and raised and to think about these matters while waiting to check out. Consumers are not wrong for doing this; it is a fundamental right of the consumer to question.

— The Communication Scarcity in Agriculture, J. Eise, W. Hode (New York, N.Y. 2017) at p. 46.

Consumer concerns over the impact of modern food production on health and the environment have helped drive the popularity of Process Labeling. The Council for Agricultural Science and Technology, a nonprofit scientific organization, recently assembled a cross-functional panel of experts to assess the phenomenon and make policy recommendations. The panel concluded:

Under appropriate government oversight, these ‘process labels’ can effectively bridge the information gap between producers and consumers, satisfy consumer demand for broader and more stringent quality assurance and ultimately create value for both producers and consumers.

The mounting popularity of Process Labeling is readily apparent. In the U.S., consumer purchases of organic products have reached record levels, amounting to over $43 billion last year, and up 11% over the previous year. The demand for environmental or “eco” labeling is robust, with more than 460 different labels relating to 25 industry sectors now in use in nearly 200 countries. Food companies are embracing Process Labeling in the name of “transparency,” with many committing to provide more information – via labeling – about how food is produced.

Execution Challenges

While Process Labeling has great appeal and potential utility, execution can be difficult for three reasons.

First, such labels require a “process” clearly defined by a standard fixed either by the government or a well-established, independent agency. The standards for organic farming set by the National Organic Program are the leading example of such a third-party standard.[1] USDA’s systems of grading meat, poultry, butter and eggs, and requiring Country of Origin Labeling (“COOL”) are other examples of clearly defined process standards. Sellers, buyers, trade groups and industry associations have also established quality standards and guidelines against which Process Labeling claims can be assessed.[2] However, it is hard, if not impossible, to find widely accepted, well-established definitions for some of the most popular process claims such as “cage-free,” “grass-fed,” “free range,” “naturally raised,” and many others.

Second, even with a defined standard, substantiating Process Labeling claims can be challenging, especially for large-scale operations with far-flung suppliers. Adequate substantiation requires supply chains operating under strict control, with rigorous oversight and continuous monitoring. The food producer must maintain strong and transparent supplier relationships and check in frequently to assure that the operation is running as agreed and without errors or gaps. Independent verification is helpful, and producers can obtain that kind of help from the USDA’s Agricultural Marketing Service, which provides a wide variety of independent verification services through its Process Verified Program (“PVP”), a voluntary, user-fee-funded program. The PVP uses highly trained auditors to conduct inspections, review processes and documentation and thereby assure that a producer is adhering to the standards supporting the process claim.

Third, Process Labeling can send inferential messages about health or well being that can be highly misleading without prominent disclaimers or other disclosures. The Federal Food, Drug, and Cosmetic Act (“FFDCA”) provides that a food is misbranded if its labeling is “false or misleading in any particular.” The FFDCA has long been interpreted as holding a producer strictly accountable for the claims made in labeling. This includes accountability for omissions, as the FFDCA empowers FDA to find a label misleading if it fails to reveal facts that are “material” in light of the representations that are made for the product.

GMOs are a case in point. A recent consumer survey concluded that an overwhelming majority of consumers worldwide think non-GMO foods are healthier than foods made with GMOs. However, FDA has found no scientific basis to require labeling because GMO foods are safe and not materially different from non-GMO foods. Now consider whether the following claims should appear right alongside each other on a food’s principal display panel:

Healthy / Non-GMO

Is this lawful? Or does the implication that non-GMO foods are healthier violate the FFDCA by failing to disclose the scientific consensus that GMOs are safe and that avoiding them does not brings a health benefit? Information necessary to avoid misleading consumers should be provided at the point where the claim is made. In this case, the label should have noted the FDA’s position on the same panel, or at least on an adjoining one.

Conclusion

Process Labeling can inform consumers about the origins of their food and the methods by which it was produced, and in doing so promote a sense of interconnectedness and a better understanding of agriculture. However, such labeling requires clearly defined standards and significant investments in supply chain oversight and monitoring. Process Labeling claims can mislead consumers about benefits where none exist.

The CAST panel, while seeing the upside of Process Labeling, recommended strict regulation. Labelers should explain the scientific significance of the process (“GMO corn for reduced pesticide use”) and disclose when there is no benefit (“rBST-free / No significance difference has been shown in milk from non-rBST cows”). Such standards of care can certainly help unlock the potential of Process Labeling to educate consumers and help them feel just a bit closer to their world and the ways in which their food is made.

EAS Offers U.S. Agent Services for Foreign Companies

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The FDA’s regulatory requirement for foreign firms to have a U.S. Agent can be confusing, to say the least. There are very specific requirements for foreign firms to have a U.S. Agent, and failure to have a competent and responsive U.S. Agent can cause significant compliance issues, delays in applications and submissions and can even impact the importation of their product into the United States. The information below is provided to offer clarity to these requirements and help firms understand this area of the FDA’s governing requirements.

For FDA purposes (as defined in section 201(e) of the Federal Food, Drug, and Cosmetic Act), a U.S. Agent means a person who is physically residing or maintaining a place of business in the United States. A U.S. agent cannot be in the form of a mailbox, answering machine or service, or another place where an individual acting as the foreign facility’s agent is not physically present. U.S. Agent is not the same as a shipper’s U.S. Agent for CBP (Customs and Border Patrol).

What does a U.S. Agent do? Your appointed U.S. Agent will become your firm’s first point of contact with the FDA. They will facilitate communications between your company and the FDA in the area of applications, site inspections, regulatory notifications and resolution of formal compliance concerns (FDA 483s and Warning Letters).

This is particularly beneficial when time zones put your normal operating hours out of synch with the FDA’s routine working schedule. For all human and animal drug application holders and sponsors (DMF, VMF, NDA, BLA, ANDA and NADA, etc.) the U.S. Agent can work to assist and coordinate the migration to electronic submission filing submitting your Amendments, Supplements, Annual Reports, LoAs, etc. via the FDA ESG system.

The FDA eCTD requirements for submissions to CDER and CBER went into effect May 5, 2017, for NDAs, ANDAs and BLAs and will go into effect May 5, 2018, for DMFs and INDs. Submissions of 10 GB or smaller MUST be sent via the FDA ESG. After these dates, only submissions greater than 10 GB will be accepted via physical electronic media.

Who is required to have a U.S. Agent? All foreign establishments and firms who wish to ship their products into the U.S., firms who have an active regulatory submission or are required to be registered with the FDA are expected to have an appointed U.S. Agent. This includes any drug product applications (INDs, NDA, ANDAs, BLAs, NADAs, DMFs, VMFs, etc.) whether pending or approved, the distribution of drug substances, intermediates and finished dosage forms into the U.S. for either commercial or research and development purposes.

A U.S. Agent must be identified for every single foreign facility registration. This includes food facilities (21 CFR 1.232 (d)) under which dietary supplement facilities fall (21 CFR 1.227), drug establishments (21 CFR 207.40 (c)) and medical device facilities (21 CRF 1.232 (d)). A U.S. Agent appointment is required for all ANDAs (21 CFR 314.95(7)) and NDAs (21 CFR 314.52(7)) as well as foreign color manufacturers (21 CFR 80.21(d)). It is highly recommended, although not necessary, to have a U.S. Agent appointed to your DMFs. While INDs do not require a U.S. Agent, it is certainly beneficial to have one.

When is a U.S. Agent required? The U.S. Agent must be appointed before any registration, application or communications with the FDA can begin. As a foreign firm, at the time of registration and listing, you will be asked to provide the name and contact information for your U.S. Agent. Likewise, at the time of submission of any application to CDER, CBER, CDRH, an appointment letter must accompany each specific submission and be on file with the FDA to facilitate any communications.

EAS Consulting Group offers the full breadth of U.S. Agent services to clients around the globe and we are prepared to assist you with meeting the regulatory requirements in this area. Let us know how we can help you.

The Food Processing Industry’s Newest Challenge: Safe Quality Food’s Edition 8.0

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The Safe Quality Food Institute (SQFI) is coming close to releasing its long-anticipated Edition 8.0. While many things could change during the final review and “sign-off” by the SQFI Technical Advisory Committee and SQFI staff, it is likely that the new SQF Edition 8.0 will have the following formatting and content changes. Some of these changes make the new Edition 8.0 more closely aligned with the FDA’s Preventive Controls for Human Foods (PCHF) regulation.

SQFI has indicated that Edition 8.0 will be enforced by SQF certification bodies six months after the implementation date (expected April 1, 2017). If SQFI meets its final publication schedule, all SQF-certifications after October 1, 2017 will have to have incorporated all Edition 8.0 changes.

Formatting Changes:

  1. Edition 8 has divided the food safety requirements in Edition 8 into specific food sectors as follows:
    • SQF Food Safety Fundamentals (applies to all food processors)
    • SQF Food Safety Code for Primary Production
    • SQF Food Safety Code for Manufacturing
    • SQF Food Safety Code for Storage & Distribution
    • SQF Food Safety Code for Food Packaging
    • The SQF Retail/Wholesale Grocery Code
    • The SQF Quality Code (Formerly Level 3)
  2. All food quality requirements have been incorporated into a separate “SQF Quality Code” and all previous food safety items have been relocated into the specific “SQF Food Safety Codes”.

Specific Operational or Substantive Changes:

  1. Levels #1, #2 and #3 have been eliminated.
  2. A food processor may forgo the unannounced certification audit once during each three (3) year cycle and voluntarily choose to move to annual unannounced recertification audits. Locations with annual unannounced recertification audits shall be recognized on the SQFI Certificate as an “SQFI Select Facility.”
  3. All products produced, stored or processed on site shall be included on the site’s certificate, unless exempted. The site must demonstrate that exemptions that are either site or product specific as part of the scope of certification do not put certificated product at food safety risk.
  4. The requirements for a food processor’s “Environmental Monitoring” have been expanded, similar to the FDA FSMA “Preventive Controls for Human Foods (PCHF)” requirements:
  5. SQFI and the certification body must be notified by the food processor in writing within 24 hours of becoming aware of a food safety problem that requires public notification. SQFI can be notified at foodsafetycrisis@sqfi.com.
  6. The site and the certification body shall agree on the audit scope before the certification audit begins. The agreed upon audit scope cannot be changed once the audit has commenced.
  7. The certification body must advise the supplier (food processor) of the name of the SQF food safety auditor at the time that the SQF audit is scheduled.
  8. In instances where a food processing plant has some operational written procedures or records kept or managed by the corporate office, the SQF audit may need to be conducted at the corporate office location as well as at the food processing plant location.
  9. The definition of “critical nonconformity” has been slightly expanded to include the failure to meet food safety regulations such as state, USDA or FDA regulatory actions.
  10. The section on “Food Defense” is now titled “Food Defense and Food Fraud”.
  11. Significant new requirements on allergen management have been added, consistent with the FDA FSMA “PCHF”.
  12. If a food processor chooses to not implement any Module 11 GMP-like requirements, the reason for not implementing must be submitted in writing to the certification body prior to the audit.
  13. Water requirements have been strengthened. Water stored on-site must be routinely monitored and water used as an ingredient in processing or for equipment cleaning and sanitizing must be treated, with water microbiological samples be taken annually.
  14. Lighting in food processing and handling areas and at inspection stations shall be at an average illuminance of 200 lux, or as required by applicable regulations.
  15. A current list of all chemicals used in the food processing plant is now a requirement.
  16. All ventilation equipment and devices in product storage and handling areas shall be adequately cleaned to prevent unsanitary conditions.
  17. There are significant new written and operational requirements related to maintenance of the processing facility and processing equipment.

For more insight on the new SQFI Edition 8.0, contact Allen Sayler, EAS Senior Director of Food & Cosmetic Consulting Services at 571-48-5509 or asayler@easconsultinggroup.com.

EAS Consulting Group is a licensed SQFI Training Center and has scheduled SQF Edition 8.0 training sessions. EAS can also provide on-site SQF-based assessments by SQF-registered consultants.

Understanding the Drug-Cosmetic Conundrum When Marketing Your Products

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Products marketed as cosmetics can easily find themselves the target of FDA compliance action based on improper claims and statements.

FDA is charged with enforcing the laws and regulations that ensure the safety and labeling of products, including cosmetics, that account for 20 – 25 % of all U.S. consumer spending.

Cosmetics were first regulated under the 1938 Federal Food, Drug and Cosmetic Act (FFDCA). They are defined as “(1) articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body or any part thereof for cleansing, beautifying, promoting attractiveness, or altering the appearance, and (2) articles intended for use as a component of any such articles…”.

By comparison, drugs are defined as articles (1) intended to treat or prevent disease or (2) that affect the structure or function of the body. Cosmetics are products that provide mostly superficial effects that do not include “nutrition” as with foods or that “treat or prevent disease or affect the structure or function of the body” as with drugs. Because of the narrow definition and generally low safety risk for cosmetics, they can be marketed, with the exception of color additives, without pre-approval by FDA.

As with all products regulated by FDA, cosmetics must be safe and properly labeled. A cosmetic is considered unsafe (adulterated) if (among other things) “it bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling thereof, or under such conditions of use as are customary or usual…”. Also, cosmetics must be labeled in accordance with the applicable laws which include the FFDCA and the Fair Packaging and Labeling Act (FPLA).

Under this regulatory framework, a product can be classified as both a drug and a cosmetic. Product classification depends on the intended use which is determined based on claims made for marketing the product and whether or not the statements fit the definition for cosmetics and/or drugs. Because of the difference in the regulatory schemes for cosmetics and drugs, FDA has sought over the years to make sure that a marketed product stays within the established boundaries that apply. For example, a cosmetic may not make claims that the product will treat and prevent a disease or alter the structure or function of the body.

So how does one tell what claims pose a risk that a product will be classified as a drug and subject to FDA compliance action? This is a complicated question and there are no quick, easy answers. Product classification does not necessarily depend on the presence of a single word or phrase and FDA will typically make a determination based on all product statements and representations or “claims” taken together. FDA’s Warning Letters provide the most readily available source of information on claims.

Let’s look at what types of claims are problematic based on recent warning letters. Many problem claims relate to a structure or function of the body (skin) which is appropriate for a drug rather than a cosmetic.

A warning letter dated October 18, 2016, based on an establishment inspection and a website review, noted:

  • The product label said, “It stimulates cell-cell interaction, assists in the formation of collagen, and increases skin elasticity…”
  • The website included the claims “Stimulates cell-cell interactions, and accelerates cell renewal” and “Helps to preserve cellular energy, assists the formulation of collagen and strengthens in structural proteins”
  • The product insert included the claims “[I]nduces signal transduction…reconstructs protein structure…acts as a topical Botox…”, “[S]timulates cell respiration and increases cell turnover.”, “[A] biosafe alternative to Botox, it relaxes muscle contraction…” and “Increase Microcirculation”.

A warning letter dated September 20, 2016, based on a website review, cited the following claims:

  • “Lemon, a powerhouse of vitamin C…with its antibacterial properties, and boosts collagen production…It also lightens age spots…”
  • “By increasing blood flow…”
  • “Organic shea butter is a powerhouse… has natural anti-inflammatory properties that can take the sting out of insect bites.”

A warning letter dated April 14, 2016, based on a website review, noted:

  • The product website included the claim – “Removes Wrinkles Instantly”
  • Product Ingredient Claims – “Tests using a 0.5% concentration of the culture have shown a clear reduction of uneven pigmentation and obvious lightening if the skin.”
  • “A super anti-oxidant …eliminates age spots, contains protection from ultraviolet A and B and boosts collagen synthesis.”

As you can see from these examples, products marketed as cosmetics can attract FDA compliance action based on improper claims and statements. The FDA issued more than 29 warning letters to cosmetic firms in 2016.

EAS labeling experts are available to assist with the regulatory compliance of claims for cosmetic products.

Using Temporary Marketing Permits for Food Products

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FDA food standards of identity are regulations that establish the names and define the basic nature of certain foods. Food standards prescribe, among other things, what ingredients are required or optional and may describe the manufacturing process when that process has a bearing on the identity of the food. If a food is labeled with the name that is included in a food standard of identity, it must comply with that food standard. If it does not meet the standard, it is a non-compliant food product.

So, how can you market foods that have food standards of identity if you want to use a new ingredient or new technology not included in the food standard? You have to either ask FDA to revise the food standard regulation or you must use a different name. However, if you want to use the name specified in the food standard regulation, you can still market a product that deviates from the food standard if you obtain a temporary marketing permit (TMP). A TMP is permission to market a food under a standardized name that deviates from that food standard of identity.

FDA recognized that prior to revising a food standard, market testing is needed to assess the feasibility of making the change and to test for consumer acceptance of the food. Therefore, it established procedures for TMPs that allow manufacturers to market test their products before a standard of identity is revised.

Manufacturers may request a TMP under regulations in 21 CFR 130.17. This regulation requires manufacturers to submit certain information with their application, including information about the applicant, a description of the deviation from the food standard, a statement on how the deviation is advantageous, and proposed labels for the food.

FDA will evaluate the information provided in the TMP application to see if any new ingredient is safe and determine whether the manufacturer has given a rational basis for the deviation from the standard. If FDA grants the TMP, it publishes a notice in the Federal Register granting the TMP for 15 months. The TMP will expire in 15 months from the date the product first enters interstate commerce, but can be extended by application to FDA. When applying for an extended TMP, the applicant must simultaneously submit a petition to revise the food standard regulation. If FDA grants the extension, it publishes a notice in the Federal Register and invites other interested parties to market the product. This extended TMP is in effect until FDA makes a ruling on the petition to amend the food standard.

It is important to note that FDA thoroughly reviews the TMP to determine if there is a rational basis for the deviation and that consumers are not misled by the name or label. FDA also reviews the labels for compliance and needs to accept the labels prior to granting the TMP. Receiving a TMP is an important step in revising food standards to address innovation. EAS consultants are available to assist manufacturers in applying for a TMP.

Recent Developments in EU Food Regulation

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As part of a new series in EAS-E-News on services provided through EAS partnerships, Italy-based food technology and consulting firm Almater shares the following insights on regulatory developments in the EU in the area of foods, including so-called novel foods.

The European Union has significantly revised its legal and regulatory framework for novel foods in recent years, as well as its requirements for labeling, presentation and advertising of food.

The EU updated its 1997 regulation on novel foods with the adoption of a new novel food regulation (No 2283/2015) on November 25, 2015. The regulation, a centralized authorization procedure for novel foods at EU level, offered new provisions on nano-ingredients and on “insect-food,” and a simplified authorization procedure for “traditional products” from third countries. It also clarified requirements for food produced from cloned animals.

Under EU law, a “novel food” means any food that was not used for human consumption to a significant degree within the Union before May 15, 1997. Genetically modified foods fall within a different regulatory framework, as do food additives, enzymes, flavorings and extraction solvents. Some food categories may fall within the scope of the novel food regulation, requiring a prior-authorization to access the EU market. These include: food with a new or intentionally modified molecular structure (for instances a patented synthetic polymer); food from microorganisms, fungi or algae (such as extracts obtained from a mycelium cultivated in a submerged fermentation), food from plants or their parts, or from animals or their parts (for instances lipid extract from a specie of krill), food from cell culture or tissue culture (upcoming cultured meat, for example).

The novel food regulation also includes food consisting of engineered nanomaterials, food consisting of, isolated from or produced from material of mineral origin and food resulting from a new production process.

From January 1, 2018, the EU marketing authorization procedure will be centralized at the European Commission, which will evaluate novel food applications taking into account the European Food Safety Authority’s risk assessment and “other legitimate factors.” The current individual licensing authorizations will be replaced by generic permissions.

The novel food regulation allows applicants protection – for a limited time – for new scientific evidence and proprietary data provided in support of an application for inclusion of a novel food in the EU list. The regulation also includes a simplified authorization procedure for traditional foods from third countries that have historically proved safe for food use.

The novel food regulation includes a better definition and ad hoc provisions on nano-ingredients. As the term “engineered nanomaterials” is currently defined in Regulation (EU) No 1169/2011, nano-ingredients are considered novel foods under EU law. The Commission is called upon to reformulate this definition to reflect scientific and technological change and internationally agreed definitions. EFSA and EU Member State risk assessors are working to enforce scientific and regulatory framework on nanoscience and nanotechnologies in the food and feed chain. The novel foods regulation provides a clear opening for the use of whole insects and their parts in foods, if they pass an EFSA risk assessment.

Regulation (EU) No 2283/2015 entered into effect on January 11, 2016 and will become fully applicable from January 1, 2018, except for certain provisions.

EU regulatory framework on food information

The EU’s regulation on the provision of food information to consumers (No 1169/2011), which went into effect in December 2014, will be fully applicable from December 2016 for nutrition declarations on prepacked food.

A cornerstone of food labeling in the EU market, this regulation requires new mandatory information on allergens and nutrition. In addition, it includes new requirements for specific products such as nano-ingredients, refined oils/fats of vegetable or animal, de-frozen foods or formed fish/meat etc.

The regulation also broadens the role of the European Commission.