FDA Responds to Comments in FSVP Final Rule

FDA released three significant FSMA final rules last month, on foreign supplier verificationproduce and accreditation of third-party auditors – all formally published in the Federal Register on November 27.

Each of these three significant rules deserve separate commentary, so I will first consider the FSVP rule in this article and comment separately on the accreditation and produce rules in upcoming issues.

The agency plans to issue two more final rules, on sanitary transportation and on intentional adulteration, by May 31, 2016. These two rules, along with the final rules on preventive controls for human and animal foods published on September 17, will complete what the agency calls the “seven foundational final rules” implementing the Food Safety Modernization act (FSMA).

As is required in final rules, in each of the new rules FDA responds to the numerous public comments and explains why it did or did not make requested changes in the final versions. The 128-page FSVP rule, for example, includes 334 specific responses to comments.

FDA says the FSVP requirements are intended to be “sufficiently general and flexible to apply to a variety of circumstances without being unduly burdensome or restrictive of trade.” For example, the final FSVP rule adds flexibility by not requiring an importer to conduct supplier verification when the hazard will be controlled by a subsequent entity in the distribution chain in the United States.

Responding to comments, the agency declined to extend the effective date of the rule beyond the customary 60 days after publication of the final rule in the Federal Register. So the FSVP rule will be effective from January 26, 2016. But it did agree to revise the 18-month compliance dates for some circumstances.

Some comments had asked the agency to set uniform compliance dates for all the FSMA rules, to help businesses plan for the extensive changes. The agency was receptive to this request and says it wants to align the FSVP compliance dates with the compliance dates of the supply-chain program provisions in the preventive controls regulations “to the extent feasible.” In the FSVP final rule, the date that importers must comply with the regulation is the latest of the following dates:

  • 18 months after the publication of the final rule;
  • For the importation of food from a supplier that is subject to the preventive controls regulations for human food or animal food or the produce safety regulation, 6 months after the foreign supplier of the food is required to comply with the relevant regulations; or
  • For an importer that is also subject to the supply-chain program provisions in the preventive controls regulations for human food or animal food, the date the importer, as a receiving facility, is required to comply with the supply-chain program provisions of the relevant regulation.

The agency also revised other elements of the proposed FSVP rule in response to comments. For example, because the requirement to perform supplier verification on an establishment that manufactures/processes, raises, or grows an imported food could impose a greater burden on importers when the foreign supplier is not the immediate source of the imported food – such as for consolidated raw agricultural commodities (RACs) – the agency revised the rule to allow an importer of a food to obtain information needed to meet certain FSVP requirements from other entities, such as a distributor or consolidator of the food.

The final rule also excludes from most FSVP requirements certain types of food from a foreign supplier in a country whose food safety system FDA has recognized as comparable or equivalent to that of the United States if:

  • The food is within the scope of the relevant official recognition or equivalency determination;
  • The importer determines that the foreign supplier of the food is in good compliance standing with the relevant food safety authority; and
  • The food is not intended for further processing in the United States, e.g., packaged food products and raw agricultural commodities (RACs) that will not be processed further before consumption.

The final rule also establishes modified FSVP requirements for very small importers and importers of food from certain small foreign suppliers. The agency has aligned the definition of “very small importer” with the definitions of “very small business” in the final rules on preventive controls for human food and animal food.

Depending on the circumstances, supplier verification activities could include audits, records review, sampling and testing, some combination of those, or other activities, FDA says. Importers have the flexibility to use a different approach if they can establish that it will provide adequate assurance that the foreign supplier is significantly minimizing or preventing the hazard.

Importer facilities in compliance with the supply-chain program requirements under the preventive controls rules would be deemed in compliance with nearly all of the FSVP requirements, the agency says. The “importer” is the United States owner or consignee of a food offered for import into the United States, or – if there is no United States owner or consignee at the time of U.S. entry – the importer is the U.S. agent or representative of a foreign owner or consignee of the food offered for import at the time of entry, as confirmed in a signed statement of consent.

There may be many circumstances in which an importer evaluates the hazards in a food and determines that there are no hazards requiring control. In these cases, FDA says, the importer would not be required to conduct a supplier evaluation. Examples of foods for which there might not be hazards requiring controls include salt, many kinds of crackers, many cookies and many types of candy, bread, dried pasta, honey, molasses, sugar, syrup, soft drinks and certain jams, jellies and preserves, the agency says.

FDA has prepared a one-page decision-tree, titled Am I Subject to FSVP?, which may be a good place to start if you are uncertain whether your activities are covered by this rule.

Getting to Grips with the electronic Common Technical Document (eCTD) Process

By Albert Yehaskel

Completing a successful electronic Common Technical Document (eCTD) submission can be daunting, even with the help of guidance documents from the International Conference on Harmonization (ICH) – which developed the eCTD – or from the Food and Drug Administration.

The success or failure of an eCTD submission depends greatly on processes put in place prior to beginning the process. First, it is necessary to ensure that the company has what’s needed to assemble an eCTD. If the manpower, knowledge, experience and hardware/software are not in place, failure is almost a certainty. These should be sourced from outside if necessary.

Once these are in place, it is imperative to set a timeline. The timeline is constructed by picking a realistic filing date and working backwards to see what needs to get accomplished to meet that deadline. The timeline will be part of a Global Development Plan that will change and be revised but will remain your “road map” for several years.

The eCTD is made up of five modules:

  • Module 1 provides for administration information and is country specific. For example, submissions in the United States require a Form FDA 356h with specific information. Other required forms include Field Copy Certification, Patent Certifications, Financial Disclosures, and Environmental Assessment, to name a few. In the EU, different information is required, such as Consultation with Patient Groups, Pharmacovigilance, Risk Management, and other information associated with the EU Region. Canada also has its own specific requirements.
  • Module 2 provides for quality, non-clinical and clinical summaries.
  • Module 3 provides for CMC information on the drug substance and drug product.
  • Module 4 provides for non-clinical data and reports.
  • Module 5 provides for clinical data and reports (including the ISE and ISS).

In beginning to populate Module 3 and subsequently Module 2, some of the challenges that you will be faced with will include the following:

  1. Key API characteristics.
  2. Pre-formulation and formulation development programs.
  3. Ensuring that your specifications and analytical assays are well developed.
  4. Ensuring that your early and later batches of clinical trial material and commercial material are produced pursuant to Good Manufacturing Practices.
  5. Having a good stability program in place with established stability protocols.

For your non-clinical program you will need to ensure that all the appropriate animal studies have been completed pursuant to good clinical practices and each non-clinical document signed off. Once Module 4 has been populated, you will need to provide a summary of your non-clinical data in Module 2.

For your clinical program, you will need to ensure that all the requisite trials are completed on time, Clinical Study Reports (CSRs) are written and signed off and that you begin the process of writing the Integrated Summary of Effectiveness (ISS) and the Integrated Summary of Safety (ISE). Gathering all the adverse events that transpired through your program is essential. When Module 5 is completed, you will need to provide a summary of the clinical information in Module 2.

As you begin to accumulate information, data reports, you will need to identify, in synch with your development plan, potential issues that could put your program at risk. When these risks have been identified and prioritized, you will need to find ways to mitigate the risks in order to meet your timeline.

It is advisable to form an eCTD Dossier Team early on in the process and assign responsibilities to each member with deliverable dates. For example, who will be responsible for writing the various Drug Substance and Drug Product templates in Module 3? Will the same person be writing the overall summary in Module 2? Will this be an individual or a team effort? Who will write the overall nonclinical and clinical summaries once all the data and reports are in? The same applies for the ISE and ISS which are among the final documents in the process.

Careful coordination is needed to ensure on-time delivery of all the moving parts within the eCTD. It is important to keep the following documents in mind:

  1. A time line chart that needs to be reviewed and possibly modified often.
  2. A Development Plan.
  3. A list of risks and mitigation strategies
  4. A Gap Analysis
    1. Identifying documents, information and data missing in each module
    2. Prioritizing and establishing a timeline for how the missing information will be obtained and when the information will be available
    3. Identifying key issues that could derail your submission and resolving these issues quickly
  5. A tracking chart of the status of all components of the eCTD. This can include a detailed eCTD Table of Contents as well as separate tables of contents for each of the modules.

As you move forward with the eCTD process, be sure to communicate often with the FDA or Boards of Health in discussions that help address any issues that arise. Don’t leave these interactions for the end, because this will just guarantee setbacks.

As a final tip, make sure to version all your documents. There will be hundreds of them. This is a great tracking tool and will have big pay offs.

FSMA Implementation Enters a New Phase

The Food and Drug Administration hosted a public meeting in Chicago on October 20, 2015 to discuss the recently released final rules on preventive controls for human and animal food, along with plans for the next phase of FSMA implementation. This was a substantive meeting and I encourage you to view the six slide presentations on FDA’s FSMA website.

The first phase of FSMA implementation – the release of final FSMA regulations and related guidance and policies – is moving swiftly forward. FDA released final rules on preventive controls for human and animal foods on September 17 and the agency is now developing numerous guidance documents.

FDA was under a court-imposed October 31, 2015 deadline for releasing three additional final rules – on produce, foreign supplier verification and accreditation of third-party auditors (These are not yet available as I prepare this article). Under the consent decree, FDA must issue final rules on sanitary transportation and on intentional adulteration by May 31, 2016.

The second FSMA implementation phase focuses on “gaining and maintaining industry compliance,” with the final rules and identifying metrics for measuring success. The third phase involves actually using those measuring tools and making any needed adjustments.

Many elements of the complex rules will require further explanation and guidance. In the October 20 meeting, Dan McChesney, director of the Office of Surveillance and Compliance in FDA’s Center for Veterinary Medicine, presented an overview of the animal food final rule and explained, for example, that feed mills may or may not be required to comply.

Mills that are not part of a farm and are required to register as a food facility are subject to the new rule. Examples include an independent feed mill, a feed mill that makes food for contract farms, an on-farm feed mill that makes food for animals under different management than the farm, he said.

Feed mills that are part of a farm are exempt from registering as a food facility and are not subject to the new rule, he explained. For the feed mill to be considered part of the farm, the raising of animals and the feed mill must be under the same management in one general location, and animal food made at the mill must only be fed to animals under the farm’s management, he said.

The agency is currently working on several guidance documents relating to the animal food rule, including guidance on current good manufacturing practices, on human food by-products for use as animal food, and on hazard analysis and preventive controls. It is also developing a compliance guide for small or very small businesses. Under the rule, a very small business is defined as one with an average of less than $2.5 million in annual sales of animal food, plus the market value of animal food held without sale. A small business is defined as one with fewer than 500 full-time equivalent employees.

Provided the three final rules on produce, foreign supplier verification and accreditation of third-party auditors are available, I will offer my perspective on those in the next EAS-e-News issue.

New Drug Development in the 21st Century

By Nancy Chew

Most people who work in the pharmaceutical industry know that drug development comprises of pharmaceutical development, animal pharmacology and toxicology studies, and clinical research; many also know that there are quality standards applied to manufacturing and controls that become more and more stringent as the development process evolves. Similarly, the quality standards for animal pharmacology, safety pharmacology and toxicology are implemented in a tiered manner. Clinical research, the most time consuming and costly part of the process, is also controlled by quality practices.

Many more drugs fail during development than make it to market. The Pharmaceutical Research and Manufacturers of America estimates that it requires more than 10 years and $2.6 billion dollars for a drug to be approved for marketing. And only 12% of drugs that enter the development process make it to market. The discovery of clinical lead compounds requires many more potential drugs to be discarded prior to IND development.

This means that FDA holds many more pre-IND meetings than end-of phase 2 or pre-NDA meetings.

Many people hold that “regulatory efficiency” is an oxymoron. The only efficient path to market is to do it right in the first place. FDA provides consultation to pharmaceutical manufacturers throughout the development process. Using the opportunities offered by standard development, pre-IND, end of Phase 2, and pre-NDA meetings with the agency gives sponsors access to the wealth of information FDA has gained from review of previous applications as well as up-to-the minute advice on how to comply with current regulations and standards. There are published guidance documents on how to prepare for and hold these meetings; however, often, a sponsor requires the assistance of consultants who are experts in the various aspects of development that pertain directly to their product (e.g. a new nanotech formulation). Most sponsors also benefit from the assistance of regulatory experts for defining the topics and detailed questions to discuss, preparation of documents, regulatory protocol, and the conduct of the meeting itself.

Today, global drug development is coordinated mainly through the International Conference on Harmonization (ICH) process. The beauty of this system is that when a drug is developed according to ICH Guidelines, the research portfolio will be accepted in all the countries that have incorporated those guidelines into their own regulatory system. For example, the group of toxicology studies required before starting clinical studies is agreed and accepted by all the countries that participate in this process. This allows one body of technical information to be accepted by health regulatory authorities in Europe, Japan, Canada and many other countries.

Because the development of a novel compound into a marketable drug is so costly and time consuming, other regulatory routes to market are available. Perhaps the best known is the Abbreviated New Drug Application, a copy of a previously approved drug, which is available after all patents and marketing exclusivity options have expired. Recently, the 505(b)(2) process has become a popular means of short-circuiting part of the drug development process; it relies, as does the ANDA process, on FDA’s previous finding of Safety and Effectiveness for a drug product.

In summary, this brief overview illustrates that there is no simple route when introducing a new drug and there is more than one possible path to success.

Preparing for FDA Foreign Drug Inspection

By EAS Senior Consultant Robert C. Fish

An FDA drug inspection can be a very stressful experience. If it is a pre-approval inspection there is a lot at stake concerning the outcome. If the company does not pass, the application (NDA/ANDA) may not be approved or the approval may be significantly delayed. But with proper preparation the stress level can be significantly reduced and the chances of a successful outcome can be greatly increased.

Foreign drug firms have an advantage over domestic U.S. companies in that the foreign firms are given prior notification concerning when the inspection will be done. This is not usually done for domestic U.S. company inspections.

In my last position with FDA as Director of the Division of Field Investigation, I was responsible for the management of the FDA foreign inspections. We found that if we did not give foreign companies prior notice we often arrived and the management staff required to complete the inspection were not present because of vacation or other travel. As a result it has been a longstanding FDA policy that foreign companies will get prior notice of planned inspections.

Foreign drug inspection pre-approval inspections are conducted under compliance program (CP) 7346.832 Pre-Approval Inspections. The three stated program objectives are:

  1. Readiness for Commercial Manufacturing.
  2. Conformance to Application.
  3. Data Integrity Audit.

Compliance Program CP 7356.002, Drug Manufacturing Inspections may be used in conjunction with the pre-approval program. The Drug Manufacturing Inspections program uses a “systems” approach to the inspection where coverage may be given to two or more of the following systems:

  1. Quality System.
  2. Facilities and Equipment System.
  3. Materials System.
  4. Production System.
  5. Packaging and Labeling System.
  6. Laboratory Controls System.

In your preparation for the inspection you should carefully study these compliance programs. They will give you good insights into what to expect. You must also conduct training of all staff that will be involved in the inspection. The compliance programs should be a part of that training and it should cover the “do’s and don’ts” during an inspection. All staff should:

  1. Support preparation efforts.
  2. Insure that work areas are orderly.
  3. Insure that all equipment and instruments are clean and calibrated.
  4. Insure that all logs and records are filled out completely, accurately, and legibly at time of performance.
  5. Answer questions honestly.
  6. Answer questions directly.
  7. “I Don’t Know” is usually acceptable (refer to person with knowledge and responsibility).
  8. Be professional.
  9. Be courteous.
  10. Be cooperative.

Staff should not:

  1. Volunteer information.
  2. Guess.
  3. Provide any misinformation.
  4. Provide any misleading information.
  5. Be confrontational or argumentative.

You should conduct “mock inspections” to help train staff. EAS Consultants often do this for companies and it is a very good exercise for inspection preparation.

You should also have an inspection plan with details concerning how all activities will be handled from the time the investigator arrives until he/she leaves. The plan should include provisions for taking notes during the inspection, maintaining copies of any documents that the investigators takes and duplicate samples if any are taken. As part of the plan, staff should be identified to accompany the investigator at all times.

The plan should also include provisions for a “war room” for use during the inspection. In the war room, staff will make a quick review of all documents provided to the investigators before they are presented. With this review, staff can be prepared to respond to questions if there are deficiencies noted in the documents and should not be surprised by the questions.

If there are deficiencies noted during the inspection the investigator will issue the FDA 483, List of Observations at the conclusion of the inspection. There normally will be daily wrap up discussions concerning the findings for the day. Those discussions can provide an opportunity to begin some corrections before the inspection is completed. The observation may still appear on the FDA 483 at the end of the inspection, but if corrections have been made the investigator will note those in the report.

If you do receive an FDA 483 at the conclusion of the inspection the investigator will have detailed discussion with management concerning the items. The investigator will expect management to say what corrective action will be taken. If possible, commitments for corrective action should be made. But be certain that whatever commitments are made can in fact be accomplished as FDA may return to confirm corrections.

If you do receive an FDA 483, a written response should be provided to FDA as soon as possible, but at least within 14 days. The response should detail all corrective actions that have been made or are planned. If there are a number of corrective actions and their completion will take considerable time, follow up status reports should be provided to FDA.

When investigators complete an inspection they prepare a written report, Establishment Inspection Report (EIR). The EIR details all of the findings of the inspection. The report is reviewed by FDA management and is classified as:

  1. No Action Indicated (NAI).
  2. Voluntary Action Indicated (company corrections should be made, but likely FDA will not take any administrative or regulatory action).
  3. Official Action Indicated. With this classification the drug application could be withheld and/or a Warning Letter may be issued.

In summary, with adequate preparation, the stress level of an FDA inspection can be decreased and the desired outcome can be made more certain. With a good plan and proper staff training you will likely have a successful outcome.

FDA Revises Definition of “Qualified Auditor” in the Preventive Controls Rule

The Food and Drug Administration released two key FSMA-mandated regulations last month — a final rule on current good manufacturing practices (CGMPs) and risk-based preventive controls for food for humans and a related final rule on food for animals. The rules were released on September 10 and formally published September 17 in the Federal Register.

FDA now plans to release numerous guidance documents to help covered companies comply with the new requirements. For human foods, the agency is preparing guidance on hazard analysis and preventive controls, environmental monitoring, allergen controls, validation of process controls, and a compliance guide for small and very small businesses. For the animal food rule, it is developing guidance on CGMPs, hazard analysis and preventive controls, human food by-products for use as animal food, and on compliance for small or very small businesses.

The new preventive controls regulations apply equally to domestic U.S. operations and to international exporters of food to the U.S. market. With this in mind, the agency has translated its fact sheets on the two preventive controls rules into 12 major languages — including Arabic, traditional and simple Chinese, Spanish, French, Italian, Japanese, Korean, Portuguese, Russian, Thai and Hindi. Given the increasing importance of imported food in the U.S. market. Effective outreach to the international community will be a key component of a successful implementation of FSMA’s preventive control principles and I believe it is one of the biggest challenges facing the agency.

For the most part, the final rules reflect the proposed and supplemental rules, but they include some revisions made in response to comments from stakeholders. In a notable revision relating to auditing of facilities covered by the new rules, FDA revised the definition of a “qualified auditor.” The final rules use the term “qualified individual” rather than “preventive controls qualified individual.”

In response to a question about the qualifications needed for a preventive controls qualified auditor, the agency said a qualified auditor might get the necessary auditing expertise in part through education, as well as through training and experience, and it revised the definition of qualified auditor. But it concluded that a person must have some actual experience in auditing to meet the definition of a qualified auditor and that the technical expertise cannot be obtained solely through education and/or training.

Further clarification of the qualifications needed by auditors will be included in a separate Proposed Rule on Accreditation of Third-Party Auditors which has yet to be finalized.

Because the new provision refers to provisions in a future third-party certification rule, FDA plans to publish a document in the Federal Register announcing the effective date of the provision once the third-party certification rule is finalized.

EAS has a network of auditors with both the training and experience needed to conduct audits to assess compliance with the risk-based preventive controls rules. They are also available to conduct a gap-analysis for facilities wishing to ensure that they will be in compliance with the new CGMP and risk-based preventives controls requirements by the appropriate deadline.

When Should a Drug Compounder Register as an Outsourcing Facility?

By EAS Senior Consultants Len Valenti and Douglass Oeller

When is it appropriate for a compounding pharmacy to register as an outsourcing facility under 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act)?

The Drug Quality and Security Act (DQSA), signed into law on November 27, 2013, introduced Section 503B of the FD&C Act, which allows for compounding pharmacies to voluntarily register as an “outsourcing facility.” But registration is not appropriate in all situations. Pharmacies that intend for all of their products to be compounded in accordance with 503B requirements may choose to register. But pharmacies that do not intend to compound all products in accordance with 503B should not register as an outsourcing facility.

In February 2015, FDA released the following five guidance documents relating to human drug compounders:

The five documents indicate the agency’s current thinking on human drug compounding issues. The guidance also reviews additional regulatory requirements for compounders and addresses Good Manufacturing Practices (GMPs) as well as compliance with United States Pharmacopoeia 797 (which provides guidelines, procedures and compliance requirements for compounding sterile preparations).

Drugs compounded in outsourcing facilities are required to adhere to cGMPs. The new law does not provide any relief for compounding pharmacies from a FDA enforcement action concerning compliance for either traditional or outsourcing facilities from an FDA inspection. Traditional Compound Pharmacies are also subject to the FD&C Act, which can be built upon an FDA investigation where the inspection finds the possibility of contamination in which a drug may become adulterated.

An outsourcing facility is able to qualify for exemptions from the FDA approval requirements and the requirement to label products with adequate directions for use, as long as outsourcing facilities meet the following criteria:

  • Must comply with cGMP requirements,
  • Will be inspected by FDA according to a risk-based schedule, and
  • Must meet certain other conditions, such as reporting adverse events and providing FDA with certain information about the products, they compound.

Beyond the cGMP requirements, outsourcing pharmacies should be aware of FDA’s criteria for identifying a violation as an unapproved drug. The criteria include any change to an FDA approved finished drug product with a different intended use or a change in the indications, dosage, route of administration, dosage form, strength or container-closure system, or misbranding because of inadequate directions for use or extra-label use. For example, an unapproved drug could be a finished approved IV drug and prefilled into a syringe without dilution, with the intent to use the drug other than the approved use. These are violations of the FD&C Act. The FDA/CDER Office of Compliance is responsible for determining whether a violation exists as an unapproved drug.

Drugs allowed to be outsourced will be published and codified by FDA, in addition to the criteria in the above guidance documents FDA has formed advisory panels to nominate a list of bulk drugs that will be permitted to be compounded.

Although there are several thousand unapproved drugs in the U.S marketplace, these drugs are exempted by grandfather statutes, such as those on pre-1938 drugs, OTC drugs, drug shortages, where FDA and States have arranged oversight. If compounded drugs are found in violation as an unapproved drug, FDA may stay silent with regard to enforcing the FD&C Act, because the agency takes a risk-based approach as part its mission to promote health.

If a compounder chooses not to register as an outsourcing facility and qualify for the exemptions under section 503B, the compounder could qualify for the exemptions under section 503A of the FDCA. Otherwise, it would be subject to all of the requirements in the FD&C Act applicable to conventional manufacturers. FDA anticipates that State boards of pharmacy will continue their oversight and regulation of the practice of pharmacy, including traditional pharmacy compounding.

There is also a concern when repackaging a drug or biological product that a change in the product’s characteristics as part of the repackaging could affect the product’s safety and effectiveness, and cause serious adverse events (SAEs). A biological product that is mixed, diluted or repackaged outside the scope of an approved Biologics License Application (BLA) is considered an unlicensed biological product under Section 351 of the Public Health Service Act and may not be legally marketed. FDA addresses the mixing, diluting or repackaging of a licensed biological product, but it does not address a biological product licensed for further manufacturing use, or to be used in a bulk drug substance.

Serious adverse event reports (SAERs) for outsourcing facilities under 503B are required of outsourcing facilities because the term prescription drug products includes any compounded drug product subject to the prescription requirements in 51 section 503(b)(1) of the FD&C Act. The agency’s AER guidance includes details on when and how to submit SAERs. For example, a 15-Day Alert Report should be submitted no later than 15 days after receiving an initial report of an adverse event.

Under the draft Memorandum of Understanding for use in agreements between individual states and FDA on distribution of compounded human drug products interstate, it is the state’s responsibility to investigate claims and report their investigation results back to FDA.

Animal Drug Compounding Guidance

In May 2015, FDA published draft Guidance for Industry #230 – Compounding Animal Drugs from Bulk Drug Substances. Dr. Douglass Oeller, EAS collaborating veterinary drug consultant, explains that the agency’s latest animal drug compounding guidance reiterates FDA’s long-standing position that sections 503A and 503B of the FD&C Act do not provide exemptions for drugs compounded for animal use.

The guidance seeks to rein in illegal compounding that competes with FDA-approved products while still allowing enforcement discretion when veterinarians must use products compounded from bulk drug substance to treat individual patients.

Legal compounding of animal drugs is restricted to re-formulation of FDA-approved human or animal drug products. This type of compounding is allowed in accordance with the regulations set forth in 21 CFR Part 530 for extra label drug use in animals.

However, FDA has always recognized that, if no drug is approved for a specific animal species or no drug is available under the extra label drug use provisions, an animal drug compounded from bulk drug substances may be appropriate. The draft guidance document provides a set of criteria for those situations. It addresses the source of bulk active pharmaceutical ingredients (APIs) and the need for an additional affirmation from the prescribing veterinarian when compounding from a bulk drug substance.

A FSMA Milestone 

Stephen Sundlof - D.V.M., Ph.D., Senior Advisor for Animal and Human Food SafetyAs I prepare this FSMA Perspective article, we are anticipating a significant milestone in the implementation of FSMA’s preventive control philosophy – release of a final rule on current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food and a separate final rule on cGMPs and preventive controls for animal foods.

Because they were developed with a high degree of transparency and collaboration between the Food and Drug Administration and stakeholders, hopefully neither final rule will contain big surprises.

But there is still a lot more FSMA work to be done. A quick review of FDA’s open dockets relating FSMA provisions indicates the size and scope of this ongoing regulatory undertaking. The open dockets include 12 guidance documents, three draft guidances and one significant proposed rule – on user fees for accreditation of third-party auditors and certification bodies to conduct food safety audits and issue certifications. Comments on that proposal are due by October 7, 2015.

The guidance includes:

  • Draft guidance for industry and FDA staff on Third-Party Auditor/Certification Body Accreditation for Food Safety Audits: Model Accreditation Standards (FDA-2011-N-0146 Comments due October 7, 2015)
  • Draft guidance for industry on FDA’s Voluntary Qualified Importer Program (FDA-2011-N-0144)
  • Prior Notice of Imported Food Questions and Answers – Edition 3 (FDA-2011-N-0179)
  • Questions and Answers Regarding Food Facility Registration (Sixth Edition) (FDA-2012-D-1002)
  • What You Need to Know About Establishment and Maintenance of Records; Small Entity Compliance Guide (FDA-2013-N-1421)
  • FDA Records Access Authority Under Sections 414 and 704 of the Federal Food, Drug, & Cosmetic Act (FDA-2011-D-0674)
  • What You Need to Know About Administrative Detention of Foods; Small Entity Compliance Guide (FDA-2011-D-0643)
  • What You Need To Know About Registration of Food Facilities; Small Entity Compliance Guide (FDA-2012-D-1003)
  • Questions and Answers Regarding Food Facility Registration (Fifth Edition) (FDA-2012-D-1002)
  • Necessity of the Use of Food Product Categories in Food Facility Registrations and Updates to Food Product Categories (FDA-2012-D-0585)
  • Questions and Answers Regarding Establishment and Maintenance of Records By Persons Who Manufacture, Process, Pack, Transport, Distribute, Receive, Hold, or Import Food – Edition 5 (FDA-2011-D-0598)
  • What You Need to Know About Administrative Detention of Foods (FDA-2011-D-0643)
  • Implementation of the Fee Provisions of Section 107 of the FDA Food Safety Modernization Act (FDA-2011-D-0721)
  • Fish and Fishery Products Hazards and Controls Guidance (FDA- 2011-D-0287)

In the next FSMA Perspective, I hope to be able to review the new preventive controls rules for human and animal food. In the meantime, I would like to draw your attention to a series of FDA instructional webinars that deal with implementing the preventive controls rules. The agency presented an August 27 session on industry best practices for supplier management. The next webinar in the series, on October 22, 2015, will deal with minimizing allergens.

FDA’s New Medical Device Regulations 

By EAS Senior Consultant Kevin Walls

The Food and Drug Administration has recently implemented two new rules that affect all medical device manufacturers, initial distributors and repackager/relabelers.

The first new rule that went into effect on September 24, 2014, but up until now affected fewer than 10 percent of medical device manufactures, initial distributors and repackager/relabelers, is the Unique Device Identification (UDI) System. The agency is phasing in the UDI system over seven years. The new rule, established under 21 CFR Part 830, requires labels and device packages of medical devices distributed in the United States to include a UDI including easily readable plain text and Automatic Identification and Data Capture (AIDC) technology – usually a bar code.

The UDI rule also requires specified product information be submitted to FDA’s Global Unique Device Identification Database (GUDID). Most of the information in GUDID will be made available to the public. According to FDA, when fully implemented, the UDI system will serve several important public health objectives:

  • It will facilitate the healthcare community, industry, and the public’s rapid and accurate identification of a device using the UDI that appears on the device’s label and device package.
  • Medical providers, patients and others will be able to more easily access important information concerning the device, thereby reducing medical errors.
  • It will allow more accurate reporting, reviewing, and analyzing of adverse event reports so that problems can be identified and corrected more quickly.
  • It will provide a standard and clear way to document device use in electronic health records, clinical information systems, claims data sources and registries, leading to a more robust postmarket surveillance system which can be leveraged to support premarket approval or clearance of new devices and new uses of currently marketed devices.
  • It will enable manufacturers, distributors and healthcare facilities to more effectively manage medical device recalls.

FDA has accredited certain Issuing agencies to operate a system for the issuance of unique device identifiers. The information contained in the UDI must also be submitted to FDA using the GUDID. The manufacturer, initial distributor or repackager/relabeler whose name appears on the device label is considered the labeler and is responsible for complying with this new requirement. The labeler must designate an individual as the Regulatory Contact, which may be an employee of the labeler or a consultant. The Regulatory Contact is responsible for making sure that the labeler meets GUDID submission requirements.

EAS Consulting Group can assist your company by playing the role of Regulatory Contact or by acting as your company’s Third Party Submitter to submit your products’ UDIs to the GUDID.

electronic Medical Device Reports (eMDRs)

The second new rule, which goes into effect on August 13, 2015, is related to electronic Medical Device Reports (eMDRs), which is covered under 21 CFR Part 803. According to the FDA “Each year, the FDA receives several hundred thousand medical device reports of suspected device-associated deaths, serious injuries and malfunctions.” The new rule requires that all MDR reports MUST be filed electronically using FDA’s Electronic Submissions Gateway (ESG). In order to submit eMDRs via FDA’s ESG, you must either set up a Web Trader Account or work with a consulting firm that has a Web Trader Account.

EAS can help you set up a Web Trader Account so you can generate and submit eMDRs, or can generate and submit eMDRs for your company using EAS Consulting Group Web Trader Account.

FDA Seeks Input on Proposed User Fees for Accreditation of Third-Party Auditors

The Food Safety Modernization Act requires the Food and Drug Administration to establish an accreditation program to strengthen foreign food safety audits. The agency issued a proposed rule for an accreditation program on July 29, 2013. In a related July 24, 2015 notice, the agency released a proposed rule that would introduce user fees to pay for the new program.

FDA anticipates issuing a final accreditation rule in October 2015 and it is inviting public comment by October 7, 2015 on the proposed user fees. The agency lists four main groups for the purposes of the “reimbursement” charges:

  • Accreditation bodies submitting applications or renewal applications for recognition in the third-party accreditation program;
  • Recognized accreditation bodies participating in the third-party accreditation program subject to FDA monitoring activities;
  • Certification bodies submitting applications or renewal applications for direct accreditation; and
  • Accredited certification bodies (whether accredited by recognized accreditation bodies or by FDA through direct accreditation) participating in the third-party accreditation program subject to FDA monitoring activities.

Under the agency’s July 24 proposal, accreditation bodies and certification bodies would be subject to application fees for the estimated average cost of the work FDA performs in reviewing and evaluating applications. Alternatively, the agency could charge an hourly rate or could use a combination of those two methods.

FDA estimates that it would take, on average, 60 person-hours to review an accreditation body’s application, 48 person-hours for an onsite performance evaluation of the applicant and 45 person-hours to prepare a written report documenting the onsite audit.

To provide a sense of the proposed fees — which the agency expects to finalize in the fall – it proposes $202 as the base unit fee in determining the hourly fee rate, prior to including domestic or foreign travel costs. With an estimated hourly travel cost of $103, the total fee would be $305 per paid hour for each direct hour of work requiring foreign inspection travel and most applications are likely to involve foreign travel. The agency proposes to set lower hourly rates for domestic travel.

The agency is also considering whether it should establish a flat fee or an hourly rate and is inviting comments on which approach is likely to work best in terms of encouraging high-quality applications.

If it bills using the actual number of hours worked, applications that are faster to review – because they are better-prepared, for example — could result in lower fees, while applications that are slower to review — because they are less organized or require more back-and-forth with the applicant — could result in higher fees, the agency notes.

Similarly, applicants that facilitate the onsite audit process and have higher quality operations would likely have shorter onsite audits than other applicants.

The agency is also considering whether it should have hourly fees for the onsite audit while maintaining a flat fee for other activities, such as the paper application review. This hybrid approach may be most consistent with how accreditation bodies currently charge certification bodies and could “provide a balance of predictability and incentives,” the agency suggests.

Along with the Foreign Supplier Verification Program, the recognition of third parties by FDA to perform audits and inspections is central to FSMA’s goal of achieving parity between domestic and imported food safety programs. By charging user fees, FDA is less reliant on Congressional appropriations, and in the process new jobs will be created in the private sector with the ultimate result of improved food safety. Sounds like a win-win-win to me!

FDA Shares Stakeholder Voices, Issues Guidance for Qualified Importers

In a significant milestone in the Food and Drug Administration’s implementation of FSMA, the agency is expected to issue a final rule next month on preventive controls for human and animal foods.

FDA released a series of videos on FSMA implementation last month featuring comments and insights from stakeholders and agency officials. Many of those speakers expressed the view – and I agree with them – that outreach and education by the agency will be the key to the successful implementation of the new requirements.

Also last month, FDA released draft guidance on the Voluntary Qualified Importer Program (VQIP) for importers of human or animal food, for companies that might become participants in the user-fee-funded program. The agency estimates that the annual fee would be approximately $16,400 for participation in the voluntary program.

The program would allow for expedited importation of food from importers who volunteer to participate. The draft guidance describes the eligibility criteria and also reviews what might cause VQIP eligibility to be revoked, as well as criteria for reinstatement. And it describes how the agency plans to set user fees to fund the voluntary program.

FDA says the program will incentivize companies to adopt robust supplier verification programs and will allow the agency to focus its resources on food shipments that pose a higher risk to public health.

The agency estimates it will take an applicant 80 person-hours to compile all the information and complete the application for the VQIP program. FDA expects that it will receive 200 notices of intent to participate in the first year. It also expects to be able to review 200 applications in the first year, depending on the available resources. It anticipates that the program will cost $3.4 million in FY 2018, including the costs of the application review process for 200 applications, the costs of conducting inspections of importers (both foreign and domestic) accepted into the program, the costs of the final determination of eligibility into the program, and annual information technology maintenance costs.

FDA is inviting comments on the draft guidance by August 19, 2015.

FDA’s New Labeling Requirements for Restaurants and Vending Machines

By Geraldine June, EAS Senior Consultant

For more than 20 years, FDA has required full nutrition information on the labels of packaged foods. Late last year, the agency published two final rules requiring calorie and other nutrition information for foods sold in restaurants and similar retail food establishments – effective December 1, 2015 – and calorie labeling for food sold in vending machines – effective December 1, 2016. The two rules implement provisions of the Affordable Care Act of 2010.

Menu Labeling

The final rule for menu labeling covers restaurants and similar retail establishments with 20 or more locations, doing business under the same name and offering for sale substantially the same menu item. The covered establishments include:

  • Quick service or sit-down restaurants
  • Take-out restaurants
  • Pizza delivery establishments
  • Food establishments in entertainment venues (e.g., movie theaters, bowling alleys)
  • Cafeterias
  • Coffee shops
  • Superstores
  • Grocery and convenience stores

Food covered by the menu labeling requirements is “restaurant-type” food, which is defined as food usually eaten on the premises, while walking away, or soon after arriving at another location and either served in the establishment or processed and prepared primarily in the establishment. Examples of such foods are:

  • Meals in sit-down restaurants
  • Foods purchased at drive-through windows
  • Take-out food
  • Food ordered from a menu or menu board at a grocery store or convenience store
  • Foods you serve yourself from a salad or hot food bar at a restaurant or grocery store
  • A muffin at a bakery or coffee shop
  • Popcorn purchased at a movie theater or amusement park
  • A scoop of ice cream, milk shake or sundae from an ice-cream store

Alcoholic beverages are covered by the new requirements if they are standard menu items on menus or menu boards in covered establishments. Foods not covered are “grocery-type” foods which are eaten over several occasions or stored for later use (e.g., whole cakes, loaves of bread), foods intended for more than one person or requiring additional preparation before eating (e.g., pounds of deli meats and cheeses, large deli salads), and certain foods bought from bulk bin cases in grocery stores (e.g., nuts, dried fruits, olives from bulk bins).

Covered establishments must post calories for their standard menu items on their menus or menu boards and on signs for self-service food and food on display and provide to the consumer additional written nutrition information for these foods upon request. The covered establishments must also post a statement concerning suggested daily caloric intake and a statement about the availability of the additional nutrition information on menus and menu boards and on the signs for self-service food and foods on display.

A covered establishment must have a reasonable basis for the nutrition information it provides and be able to substantiate the nutrient values if requested by FDA. Restaurants and similar retail food establishments must comply with the menu labeling requirements by December 1, 2015.

Vending Machine Labeling

The final rule for vending machine labeling requires calories to be posted for foods sold in vending machines operated by a person who owns or operates 20 or more vending machines. Vending machines covered by the rule include those that sell:

  • Soft drinks and packaged snacks
  • Hot and cold cup beverages
  • Refrigerated prepared foods
  • Bulk candy and nuts

The calories must be placed on a sign near the article of food or selection button or electronically. If the food item placed in the vending machine permits the perspective customer to view the Nutrition Facts or otherwise provides visible nutrition labeling at the point-of purchase (e.g., front of pack labeling), no further calorie posting is required. Manufacturers of packaged food may want to consider providing front-of- pack labeling that includes calorie declarations for their products that will be sold in vending machines so that vending machine operators are not required to provide additional labeling.

Vending machine operators must provide their contact information on the vending machine so that FDA may contact them for enforcement purposes. Vending machine operators must comply with the vending machine labeling requirements by December 1, 2016.

Detailed information on these final rules is available on FDA’s website: http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm217762.htm

EAS consultants can assist you in understanding and complying with these new menu labeling and vending machine requirements.

  • On July 9, 2015 FDA announced an extension of the Menu Labeling Compliance date to December 1, 2016.  Read FDA’s announcement here.

FDA Invites Comment on Draft Mandatory Recall Guidance

The Food and Drug Administration issued draft guidance on mandatory recalls in a May 7, 2015 Federal Register notice and is inviting public comment by July 6. The draft document presents the agency’s current thinking on how the food industry can implement the mandatory food recall provisions the Federal Food, Drug, and Cosmetic Act (FDCA) as amended by the Food Safety Modernization Act (FSMA).

In my experience as a former director of FDA’s Center for Food Safety and Applied Nutrition and of FDA’s Center for Veterinary Medicine, the voluntary system of recalls worked well in almost all situations. Nonetheless, the mandatory recall authority is a significant addition to the agency’s enforcement powers for those rare cases in which companies fail to comply with a request.

FDA’s mandatory food recall authority went into effect as soon as the landmark food safety law was enacted on January 4, 2011. The authority added in Section 423 of the FDCA covers all foods (other than infant formula recalls, which are covered separately under Section 412) that are manufactured, processed, packed, or held at a food facility that is required to register with FDA.

The amended FDCA gives FDA the authority to order a “responsible party” to recall food products if there is “a reasonable probability” that the food is adulterated or misbranded and “will cause serious adverse health consequences or death to humans or animals (SAHCODHA).”

The “responsible party” is the person who submits the registration for a food facility at which the food is manufactured, processed, packed, or held, FDA explains. A “person” is defined as including individuals, partnerships, corporations and associations. So the owner, operator, or agent in charge of a facility who is responsible for submitting the registration is also responsible for implementing and assuring the mandatory recall is performed, the draft guidance says.

The term “food” includes articles used for food or drink for man or other animals, chewing gum, and components of any such article. The term “food” also includes dietary supplements.

Among other topics, the draft guidance describes the process the agency will follow for a mandatory recall. Once it determines that the criteria for a mandatory recall have been met, it will first give the responsible party a chance to voluntarily stop distribution and recall the food. FDA says it will provide the request in writing using “an expeditious method.” If the responsible party won’t comply, the agency may order it to stop distributing the food and it will also give an opportunity for an informal hearing. After these steps, the agency may mandate a recall – and only the FDA Commissioner has the authority to order a recall, the guidance explains.

FDA says it will consider the following factors to assess if a recall is needed:

  • Observations made during inspections of the responsible party or other parties;
  • Results from sample analyses;
  • Epidemiological data;
  • Reportable Food Registry data; and
  • Consumer and trade complaints.

The agency has the authority to collect fees from a responsible party for a domestic facility or importer who does not comply with a food recall order. The fees would cover time spent by FDA conducting the food recall activities, technical assistance, follow-up checks and public notifications. In an August 8, 2014 Federal Register notice, FDA listed its fiscal year 2015 fees for reinspections and for non-compliance with a recall order, which will remain in effect through September 30, 2015 and will be revised annually. For FY 2015, the hourly rate is $215 if domestic travel is involved and $305 if foreign travel is required.

To make consumers and retailers aware of recalls, the agency says it will “ensure that a press release is published regarding the recall,” as well as alerts and public notices, as needed. These will include, at a minimum, the name of the recalled food, a description of the risks associated with the food, and “to the extent practical, information about similar articles of food that are not affected by the recall,” the agency says.

Corporate Culture Meets FSMA Compliance at the Intersection of Food Safety

By Amy Scanlin, M.S., EAS Consulting Group, LLC

When the FDA’s overhaul of food safety, the Food Safety Modernization Act (FSMA), is fully rolled out in 2016 it will be the largest change the U.S. food industry has seen. And yet with all the increased requirements for compliance there is one link that is not addressed and cannot be addressed by FDA, that of an organization’s corporate culture and employee internal commitment to getting it right.

How can the industry help further corporate culture and individuals to understand, care about and comply with their personal roles in food safety? Food safety culture is communicated not only through written protocols but through unwritten commitment to compliance and attention to detail. EAS Senior Consultants Tim Hansen, Joan Rosen and Joseph Famiglietti share their thoughts on how corporate culture affects a firm’s understanding and response to FSMA.

Food Safety Leadership from the Top Down

“There is no question in my mind that food safety leadership starts at the top,” says Tim Hansen. “There are several reasons. First, it is usually a regulatory requirement. Second, food safety concepts are not always simple so management has to implement procedures that protect food safety as the average line worker may not understand the concepts and third, a food safety problem can cause great economic harm to the producer. It is leadership’s duty to ensure that this does not happen.”

“A food company needs to have a continuous program in place to keep their employees involved with food safety,” adds Joe Famiglietti. “A problem that I’ve seen over the years is the highest ranking officer delegates quality control and training functions to certain employees and holds them responsible for ensuring these programs are successful. CEO’s need to get more involved in product safety and demonstrate their involvement to their employees. Employees need to know that food safety is critical to their jobs and that company management is playing an active role in implementing programs to ensure their products do not adversely affect the public.”

The culture of an organization plays a role, Hansen explains. “If all employees feel like they are part of the organization and the firm treats everyone fairly there is a good chance that employees will go the extra mile. Accomplishing food safety goals can be problematic when there isn’t a highly engaged work force.”

“Employees will care more about food safety when management demonstrates leadership by ‘walking the talk,’” says Joan Rosen. “Simple steps can go a long way to build trust and drive food safety commitment.” She also says that consistent communication and actions will help to convey the company’s food safety mission and vision. This can include posting reminders around the facility, or incentives for sharing examples of food safety practices and improvements with peers.

Training and Compliance – Lessons from HACCP

Hansen cites compliance lessons learned by FDA during the implementation of the 1997 Seafood HACCP rule. “Almost all the processors had findings on the FDA 483 form,” he says. Some firms clearly did not do their due diligence in conforming to the new regulations but most of problems were due to the sheer complexity of the new requirements. The processors did not really understand what FDA expected. FDA had a big learning curve in how to communicate these complexities and have largely succeeded.”

FDA is drawing on it’s experience with HACCP as it prepares to roll out new rules under FSMA. But companies will need to understand that simply conducting a hazard analysis and preparing a written HACCP plan may not be enough,” says Famiglietti. “They may need to take a closer look at their raw material suppliers and conduct more product testing and environmental monitoring to assure they are producing a safe product.”

“A lack of training is frequently the cause of errors,” says Rosen. “Training is not just a matter of sitting people down, explaining a set of instructions and then signing a paper saying ‘I attended and have been trained.’ Verifying the effectiveness of training is just as important or perhaps more important than the training itself.”

Getting it Right – Low Acid Canned Foods

Hansen, who was a Director in FDA’s Office of Seafood and the Director Seafood Inspection Program at NOAA Fisheries prior to joining EAS shares one of his many favorite examples of industry getting it right. “In the 1980’s there had been a couple of botulism outbreaks in canned salmon. These events threatened the viability of this product as consumers were justifiably wary.”

With a few notable exceptions, the industry “really rallied around the principles of food safety for Low Acid Canned Foods,” he says. “Everyone from the President of the companies to the workers on the line became very aware of the hazards associated with canning salmon and the possibility of a botulism outbreak and many important steps were taken to ensure food safety… Everyone involved in the salmon canning process understood that they needed to do more, from the line workers to the company management, to the trade association and government regulators. It is a success story for food safety since it is been over 35 years since there has been a food safety outbreak [in that industry].”

Sometimes food safety is as simple as a choice. As FDA and industry work together to further implementation and understanding of FSMA, remember that with buy-in from all levels these guidance documents will move from merely words on paper to a living document. Staying vigilant to the importance of everyone’s role will have a significant impact.

When the FDA Inspector Wants to Take Photographs

By EAS Senior Consultant Joseph Famiglietti

Managing an FDA inspection is in itself a difficult task, but what should you do when an FDA investigator wants to take photographs at your facility? Whether it is pest sightings, equipment issues, or poor employee practices, the investigator has been trained by FDA to document situations such as these with photographs which can be used as evidence in a legal action.

If you do not permit photography, it is FDA policy to list this action in the inspection report as a “Refusal.” A photography refusal may be used against a company in a future legal proceeding to demonstrate a firm’s uncooperative regulatory attitude.

Your company should have written procedures covering the use of cameras in your facility by visitors, including FDA. The FDA believes they have the right to take photographs. Their procedures direct investigators to take inspectional photographs as deemed necessary without asking for permission to do so. Guidance is also provided to inspectors on how to handle photography refusals including obtaining the contact information for the firm’s attorney or other responsible individual so FDA management can discuss the refusal with them. The current FDA procedures regarding use of the camera are discussed in the IOM, Section (http://www.fda.gov/ICECI/Inspections/IOM/default.htm). If refused, FDA may elect to obtain a warrant to take the desired photographs.

Your company may not want to allow FDA to use a camera in your facility for a number of reasons, including protection of trade secrets or concerns that the photographs may not accurately depict the conditions. Refusing to allow FDA to take photographs can cause delays in the completion of the inspection. The agency could consider this as a partial refusal of inspection and it may be viewed as a prohibited act possibly resulting in a regulatory action.

FDA published a guidance document discussing photography refusals at drug establishments as a behavior that could cause limiting of the inspection, which may result in an adulterated drug charge. The document, “Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection” can be viewed at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM360484.pdf.

Although FDA has not published similar guidance regarding photography refusals in other FDA inspected facilities such as food firms, the agency would consider a test case to establish a court ruling on this matter.

At the onset of an inspection, the investigator will probably be carrying a camera as part of FDA issued inspectional equipment. If your company is in compliance, it is likely there will be no need for photographs. With concurrence from your legal advisor, perhaps you should consider having a respectful discussion with the investigator prior to the start of the inspection explaining your company policies and concerns. If your primary concern is protection of trade secrets, perhaps the investigator will be sensitive to your needs and exercise discretion when using the camera.

If an FDA inspector does take photographs, you should always take the same pictures for your own records. Rather than outright refusing any regulatory photography at your facility, you might request to take all photographs under FDA supervision with the agency getting all original discs or film. However, investigators prefer to take their own pictures and they would probably have to obtain supervisory permission to use your photographs.

In some instances, FDA might agree to allow industry participation in taking the pictures, if the agency prefers not to obtain a warrant. FDA considers each situation on a case by case basis and you might be surprised as to what you can get by having an open and honest dialog with the agency. Although the legal issues need to be resolved regarding FDA’s authority for camera use, it would be helpful to negotiate with the agency and perhaps reach some middle ground regarding your particular situation.

FDA Briefs Stakeholders at FSMA Public Meeting


FDA officials discussed their “work in progress” toward implementing the Food Safety Modernization Act at a public meeting hosted by the agency in Washington, D.C. April 23-24, 2015.

The agency is currently considering some new inspection ideas, they explained. For example, they may introduce an inspection system that would separate violations into major and minor, depending on the public health impact. Requirements for major violations would be more stringent, such as shorter response times and increased inspection frequency. The agency is also considering a two-step approach to inspections, beginning with a data check at a company’s corporate offices in advance of an individual facility inspection, they said.

(see more details in Food Chemical News).

Effective training will be an essential component of any successful implementation of FSMA regulations and it is encouraging to see the agency moving forward with several training initiatives. It is working with the Institute for Food Safety and Health (IFSH) — which is led by former CFSAN Director Robert Brackett — on a training curriculum for the Foreign Supplier Verification Program (FSVP). This is still at an early development stage. IFSH, which manages the Food Safety Preventive Controls Alliance (FSPCA), is also developing training programs for preventive controls.

In another initiative, the agency is collaborating with the National Association of State Departments of Agriculture (NASDA) to create voluntary on-farm pre-assessments for use before the new FSMA produce rule is fully implemented.

“We appreciate FDA’s engagement with stakeholders by hosting today’s public meeting,” commented NASDA’s CEO Barbara Glenn. “While we fully support the development of a preventive food safety system, there is still more work needed to get this right,” she said.

“The successful implementation of these rules depends on active partner engagement and education of American farmers, prior to enforcement. We must strike a balance between enhancing public health and not driving American farmers away from growing the fruits and vegetables which are so vital to human health,” Glenn said.

It seems to me that a similar balance is needed for all seven proposed FSMA rules.

Welcome to Europe!

By EAS Senior Consultant Sue Oldreive

You say color, I say colour. You say “dietary supplement”, we, legally, say “food supplement.” And of course, the French say “complément alimentaire,” the Danish say “Kosttilskud” and the Italians say “Supplemento Alimentare.” With 27 different Member States within Europe, there are many more ways to say “Food Supplement.”

Although the languages may not be harmonized, the good news is that there has been much progress in the past to harmonize controls on supplements in Europe.

The publication of the Food Supplements Directive in 2002 harmonized basic controls between EU Member States, such as definitions, the forms of vitamins and minerals that can be used and warning statements for use on labels. Together with other harmonized regulations, such as those on additives, novel foods, labeling and claims, it forms a good starting point for anyone looking to market food supplements in Europe.

However, Europe is made up of countries with long traditions and strong national identities so reaching agreements on new controls can be a challenge. The Food Supplements Directive made provision to harmonize other issues relevant to dietary supplements, such as maximum and minimum levels of vitamins and minerals permitted in a daily dose and controls on other nutritional substances used in supplements, but progress on these areas has stalled. On maximum levels that has been, in large part, due to a lack of agreement on how these levels should be derived relating back to national attitude towards food supplements. Typically, countries such as the UK, The Netherlands and Sweden have had a relaxed attitude, with no upper limits set other than for a minority of substances for which there is considered to be strong evidence of a risk to health. Other countries have a history of tight limits, such as 100% Recommended Daily Allowance (RDA) per daily dose of a vitamin or mineral supplement. With such diverse starting points, it is no wonder that the debate continues. Companies looking to sell food supplements in Europe therefore need to check the limits set by each Member State in which they wish to sell.

Beyond maximum and minimum levels, some Member States have created new laws to control the use of botanical substances in food supplements, with France the latest to publish new regulations in this area. Again, until such a time that harmonization is reached, companies need to work with a local market expert to ensure the formulation of their product is compliant with the requirements of each target Member State.

When it comes to labeling your dietary supplement, the majority of the requirements are harmonized and set out clearly in both the Food Supplement Directive and the Food Information Regulations. EU Member States may have minor additional requirements which need to be checked and incorporated before notification to the local market authority and commercialisation.

Launching into Europe will take time, patience – and often a little humor to help overcome cultural differences. A complete dossier of formula, detailed raw material specifications and the proposed label declarations will go a long way towards making the process faster and smoother.

Budgeting for FSMA Implementation


Dr. Margaret Hamburg, who retired as FDA Commissioner late last month, discussed the agency’s Food Safety Modernization Act (FSMA) budget in her final appearance before a House Appropriations Committee hearing on Capitol Hill, March 4.

Mindful of pressures on the federal budget, the administration focused its budget request for fiscal year 2016 on “the most urgent needs,” she told the House Subcommittee on Agriculture, Rural Development, FDA and Related Agencies.

The agency’s budget request for FY 2016 seeks an increase of $301 million above the enacted level for FY 2015 for a total of $1.5 billion for food safety. This total includes a $109.5 million increase in budget authority and a $191.8 million increase in user fees. Almost all of the proposed budget authority increase will be dedicated to FSMA implementation, she said.

“With FDA under court order to issue many key FSMA regulations in 2015, FY 2016 is an absolutely crucial year for the investments needed to ensure timely, effective, and non-disruptive implementation,” she said.

As it implements FSMA, the agency will be taking a collaborative approach to inspection and enforcement, focusing on food safety outcomes and encouraging voluntary compliance. The largest single portion of the budget authority will go to states to better integrate, coordinate, and leverage federal and state food safety efforts, Hamburg said.

The agency’s FSMA philosophy of “educate before and while we regulate” calls for investing in guidance, education, and technical assistance for industry to support compliance efforts, especially by smaller scale farmers and manufacturers, she said.

Finally, she said, FDA must make investments in FY 2016 to implement the new import safety system, including the Foreign Supplier Verification Program (FSVP).

“The investments FDA can make with the FY 2016 budget authority request will enable the agency to maintain momentum toward timely and successful implementation of FSMA. Without these investments, implementation will be disrupted and delayed,” she said.

The FDA Center for Food Safety and Applied Nutrition is the only product center that does not receive a substantial portion of its budget from user fees charged to the regulated industries. Of the $4.9 billion requested by the Administration for FDA in 2016, $2.2 billion (45%) comes from user fees, yet the food safety program receives only 1% of its budget from user fees. In early House versions of the FSMA bills, user fees of $1,000 per registered facility were included. This was reduced to $500 per facility in subsequent versions, and eliminated altogether in the final version. With nearly 200,000 registered food facilities, user fees could have generated $200 million per year, increasing the food safety budget by 16%.

I believe the FDA food safety program will never be able to fulfill the promise of FSMA as long as its budget is limited to federal appropriations. Cost recovery user fees would go a long way toward closing the gap, but that opportunity was lost when registration fees were cut from FSMA.

With the first batch of FSMA-implementing regulations on the way this year, it would be prudent for food companies to look ahead and consider budgets for compliance with the new FSMA regulations.

With FSMA in Mind, GAO Reviews FDA’s Overseas Offices

FDA needs to adequately staff its foreign offices – where 44 percent of positions were vacant as of October 2014 — to fulfill its inspection mandate under the Food Safety Modernization Act (FSMA), according to a newly released report by the Government Accountability Office (GAO).

Under FSMA, FDA was mandated to inspect at least 600 foreign food facilities in 2011 and, for each of the next five years, to inspect at least twice the number of facilities inspected during the previous year. However, GAO explains, the agency is not currently keeping pace with that FSMA requirement. FDA officials told GAO’s researchers they do not plan to meet the FSMA mandate because of funding. The officials also “questioned the usefulness of conducting that many inspections,” GAO says.

GAO conducted an in-depth review of FDA’s foreign office operations in Canada, China, and Mexico. The locations were selected based on an analysis of the volume of food imports, the percentage of food imports refused at the border, and the number of food facility inspections for fiscal year 2013, among other factors. The review included visits to FDA’s offices in Beijing and Guangzhou, China, and in Mexico City.

This is not the first time GAO has looked into FDA’s overseas staffing. In 2010, the oversight arm of the U.S. Congress recommended that FDA develop a strategic workforce plan for its foreign offices to help ensure it recruits staff with the necessary experience and skills. “GAO continues to believe that such a plan for the foreign offices is critical to FDA’s ability to address staffing challenges,” the new report states.

“FDA has not conducted an analysis to determine whether the number of inspections in the FSMA mandate or the lower number of inspections it is conducting is sufficient to ensure comparable safety of imported and domestic food. Without such an analysis, FDA is not in a position to know what is a sufficient number of foreign inspections and, if appropriate, request a change in the mandate,” GAO says.

I believe it would be very helpful to fully staff all FDA overseas offices. But as a practical matter, I also believe direct inspection by FDA of overseas food facilities is not the key to improving the safety of food imported into the United States. Certified third party audits, the Foreign Supplier Verification Program, along with outreach and education efforts to stakeholders are likely to play a far more important role. As final regulations begin to roll out this year, FDA’s overseas offices will have their hands full simply explaining those new regulations.

Lessons Learned from the Implementation of Seafood HACCP for FSMA

By Senior Consultant Tim Hansen

One of the tenets of FSMA is the requirement for preventive systems (AKA HACCP) for all food groups regulated by FDA. Up to the time of passage of FSMA, FDA wanted preventive systems only for seafood, fruit and vegetable juices and low-acid canned foods. Since the requirement for preventive systems is about to be extended to all foods regulated by FDA it may be instructive for affected food firms to consider some of the common problems experienced by the seafood industry during the implementation of HACCP. This regulation has been highly successful and truly promoted seafood safety and consumer confidence in these products. There are several useful lessons that may make your transition to compliance easier.

  1. Unnecessary CCP’s. Implementation of the Seafood HACCP regulation came with a great deal of uncertainty for the industry.   Their response was to include a hazard as a CCP even when it did not meet the FDA “reasonably likely to occur” standard. This resulted in some cases overly complicated HACCP plans.   Firms can avoid this problem through rigorous hazard analysis and following agency guidance for the commodity being processed.
  1. Mixing sanitation controls with HACCP controls.The Seafood HACCP Regulation requires that certain aspects of sanitation be properly controlled, monitored and documented through records. While it is feasible to include these controls within the HACCP plan it is much simpler keep sanitation controls separate from HACCP controls.   A sanitation SOP is highly recommended that show how sanitation is controlled, monitored and recorded.
  1. Monitoring need to be available in their original form in an organized fashion.Inadequate or poorly organized monitoring records were a big problem. Ideally, records should not be rewritten unless absolutely necessary. Rewritten records are a red flag to FDA investigators.   If records are missing do not falsify information to fill the gaps. This could be the basis for a severe regulatory action. It is much better to perform a verification review and corrective action that is available to the investigator.
  1. If a new product is introduced to your processing operation the HACCP plan should be amended immediately.Do not wait until a convenient time as a regulator could show up at any time. Also, do not assume that the hazard analysis and HACCP plan for a similar product will be the same.   Either can result in a finding of failure to have a HACCP plan. You should start at the beginning with a proper hazard analysis and develop the plan for that product in accordance with the hazards you identify.
  1. Scientific studies used to establish a critical limit for a CCP should be readily available to the investigator.For example, a study to show the necessary heat penetration time-temperature parameters of a cooked product to achieve sufficient bacterial kill or the proper mix of salt, water and exposure time to achieve a proper level of water phase salts in a cold smoked fish products are important information for the investigator to evaluate whether the critical limit of a CCP is adequate to control the hazard.
  1. Generic HACCP plans should not be used.In the past some operations adopted a generic HACCP plan to cover their processing without performing a hazard analysis.   This often resulted in hazards being missed and a faulty plan. FDA expects that each firm will conduct a hazard analysis.   Not doing so could result in a serious charge.

FDA Highlights FSMA Implementation in FY2016 Budget Request


President Obama’s ambitious FDA budget request for fiscal year 2016 features an increase in budget authority of more than $109 million for activities implementing the Food Safety Modernization Act.

The agency received an additional $27.5 million for FSMA implementation in FY2015, despite the very difficult budget climate in Washington, D.C., so there is at least a precedent for a significant increase even while lawmakers hunt for ways to trim budgets elsewhere.

FDA says the additional budget authority will allow the agency to “implement fundamental requirements for domestic food and feed safety; acquire the technical staffing needed to support the law, including the training of new inspectors; provide the appropriate guidance to industry about the changes the law will bring; strengthen the role of the states in helping to ensure the safety of the country’s food supply; and build and implement a new import safety system.”

Michael Taylor, FDA Deputy Commissioner for Foods and Veterinary Medicine, in a February 3 FDA Voice blog, said the agency is “at a critical juncture” as Congress considers the FSMA funding. He explains that a lot of work has to be done now to ensure that the FSMA rules are implemented in late 2016 and 2017. For example, the agency plans to deploy inspectors specialized in specific food commodities. This will involve retraining of more than 2,000 FDA inspectors, compliance officers and other staff involved in food safety activities, he said.

Funds are needed now for the agency to recruit additional experts to help develop guidance and to work with industry, academia, and state extension services to ensure that their concerns are heard, Taylor noted.

The agency plans to provide funding to state agencies and public-private-academic collaborative entities, such as the Produce Safety Alliance and the Preventive Controls Alliance. It has also joined with USDA’s National Institute of Food and Agriculture in providing grants to support food safety training for small, sustainable and organic farm owners and food processors, Taylor said.

The agency plans to provide funds to states for inspector training and to boost information sharing capacity. In addition, it needs to build state partnerships and capacity to provide education and technical assistance to growers, for the produce safety rule.

For imports, the Foreign Supplier Verification Program (FSVP) presents “an enormous challenge for both FDA and food importers,” Taylor said. The program will require an increase in staff and the training of more than 400 investigative and compliance staff within the agency. It will also require extensive training and technical assistance for importers, he said.

“The bottom line is that without investment now, and sustained funding afterwards, there is the risk that the implementation of FSMA will be uneven or even delayed,” Taylor said.

This seems to me to be a fair assessment.

Verifying Label Claims “By Input” Unacceptable

By EAS Senior Consultant Tara Lin Couch, Ph.D.

The FDA regulations dictated in 21 CFR 111, Current Good Manufacturing Practice (cGMP) in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements, require that each batch of a finished dietary supplement product must meet quality requirements for identity, purity, strength, composition, and limits of potential contaminants.

Criteria used to establish that these requirements are met are supposed to be provided in a Finished Product Specification developed by the dietary supplement company. FDA issued more than 400 Warning Letter citations for inappropriate specifications in 2013 and 2014. Many of these violations were due to a failure to have Finished Product Specifications at all, but recent Warning Letters have also noted that using solely the input of a dietary ingredient for verifying the strength “By Input” is unacceptable.

The input of a dietary supplement alone is not a scientifically valid analytical test method for determining the strength of a dietary ingredient in a finished product. Chemical testing of the ingredient should be accomplished whenever possible. If that is not possible due to the unavailability of a scientifically valid test method, the testing may be exempted provided dietary ingredient raw material testing, in-process testing, other finished product testing, process controls, and additional information can support that the strength of the dietary ingredient can be verified without testing, as allowed in 21 CFR 111.75(d)(1).

The incoming dietary ingredient raw material must be verified to meet quality requirements for identity, purity, strength, and the lack of potential contaminants. Warehouse controls must then ensure that the material is held in a condition in which its quality is not altered. The material must be formulated at an appropriate amount, with sufficient overage, to meet the label claim while taking into account manufacturing variability. This is dictated in an approved Master Manufacturing Record (MMR). Once executed, the Batch Production Record (BPR) must document that the correct amount of the dietary ingredient was actually dispensed into the product during manufacture. Established in-process examinations and tests are then used to verify that the batch is uniformly mixed and meets the unit dosage weight and weight variation requirements. Variations on weight cannot exceed the overage amount to ensure that even the smallest dosage unit still complies with the label. In-process chemical tests can also be employed to verify the amount of a dietary ingredient. This can be particularly beneficial if the reason a dietary ingredient is exempted from testing is because of matrix interferences or instrumental quantitation limits.

Other finished product testing can also be used to support that an exempted ingredient is present in the product at the correct, labeled amount. Test results from chemically similar ingredients that are determined to be as expected suggest that the exempted ingredient is also present at expected levels because these ingredients will tend to react the same way during manufacture, especially if both ingredients are introduced and processed in the same step. Results obtained from finished product testing of other ingredients whose concentrations are associated with the exempted ingredient may also support that the exempted ingredient is present as expected.

Finally, the number of other finished product ingredient tests that are performed is important. If all other test results are determined to be within specification, it indicates that the product was manufactured according to the MMR and there is no reason to expect anything different from an exempted dietary ingredient.

Dietary supplement companies that are compliant with all parts of 21 CFR 111 will already be performing these activities. A procedure that summarizes the overall process of verifying the addition of a dietary ingredient can then be created and used as the test method reference on the Finished Product Specification. A separate document that describes the details of test exemptions per product should also be generated. The actual result obtained should be acquired from the completed batch production record.

The “By Input” approach is no longer relevant.

Commenters Say Re-proposed FSMA Animal Food Rule Needs Further Revision


The December 15 comment deadline on FDA’s re-proposed rule on Preventive Controls for Animal Food has come and gone. Stakeholders generally welcomed the supplemental proposal as an improvement on the original proposed rule. But further significant changes are needed, according to recent comments submitted to FDA.

Valley Proteins Inc., of Winchester, VA, one of the nation’s largest independent renderers, says in a December 8 comment that the final animal food rule should not include a “blanket requirement” for product testing for rendered products used in food for animals. Product testing has “limited value in confirming that control measures are effective” because testing in and of itself does not protect against hazards occurring in foods, the company suggests. “Rather than focusing on a testing procedure, the focus should be on adherence to the processes and controls that provide the true protection, such as maintaining the appropriate cooking temperature, etc.,” it says.

Similarly, environmental monitoring is not appropriate for many parts of the rendering process, the company contends. The process takes raw materials such as inedible meat parts and used cooking grease and converts them into fats and proteins used as ingredients in animal feeds and in biofuels. “By its nature, rendering takes raw materials that are, in a sense, contaminated and converts them into clean, safe products for use in the food supply,” says Valley Proteins’ President, Gerald F. Smith Jr.

“The final rule should not mandate environmental monitoring for rendering but should allow for the facility to determine whether such monitoring is necessary or appropriate,” he says.

West Central Cooperative of Ralston, IA, a farmer-owned group connecting producers of agricultural products to a network of processors and end-users worldwide – one of the 20 largest grain companies in the U.S. – says in a December 11 comment that the proposed rule should be “revised significantly” to reflect the intent of FSMA and “provide sufficient flexibility to allow facilities to adopt animal feed and pet food safety practices that are practical and effective for their specific, individual operations.”

The proposed rule would for the first time require current Good Manufacturing Practices (cGMPs) for food for animals, along with hazard analysis and risk-based preventive controls. The re-proposed rule also includes a new definition for the phrase “significant hazard.”

“We generally support FDA’s new proposed term ‘significant hazard,’ because it would better define those hazards for which rigorous management control activities may be needed,” says West Central’s President and CEO-elect, Milan Kucerak. “However, we believe the proposed regulation should be further revised to provide firms with appropriate flexibility to manage feed risks in a manner commensurate with the hazard,” he says.

Any product testing or environmental monitoring requirements should only be applied to significant hazards, if any, present in the firm’s operation, Kucerak says. The significant hazard approach should also be applied in the context of hazards that may be intentionally introduced into products for economic gain, as well as for supplier program requirements that the firm relies on its supplier to control, he says.

In a December 9 comment, the Michigan Agri-Business Association says it is particularly concerned that FDA’s proposed cGMPs establish reasonable and practical requirements for animal feed and pet food, and not be based on requirements necessary for human food. Many of the proposed requirements “inappropriately focus on the hygienic design and construction of equipment and facilities, and would establish standards that are required for human food. We strongly believe that FDA must make significant revisions to the proposed cGMPs so that the final regulation does not add unnecessary requirements that would cause animal feed and pet food companies to expend millions of dollars towards attempting to comply with regulatory obligations that are not need to assure the safety of animal feed, says James E. Byrum, the association’s president.

From FDA Ombudsman to EAS Consultant

By EAS Senior Consultant Les Weinstein, JD, MPA

Every Center in FDA, except CFSAN, has an Ombudsman; there is also an Ombudsman in the Office of the Commissioner. I am the only person to have served as the Ombudsman in two different Centers: the Center for Tobacco Products (CTP) for three years and the Center for Devices and Radiological Health (CDRH) for ten years, working in the Office of the Center Director in each position.

An FDA Ombudsman investigates external complaints about the agency; negotiates, mediates or otherwise facilitates the resolution of disputes between FDA and regulated companies; and responds to inquiries from stakeholders who have been unable to get answers elsewhere in FDA.

An Ombudsman, accessible to regulated industry, eases their way to being heard; listens to their issues and concerns; informs them of the regulatory process; and strategizes with them on options to challenge or appeal a decision. Often an Ombudsman is the catalyst that results in an equitable solution to a problem.

I think that having been an Ombudsman at FDA is the perfect segue to being a consultant to companies regulated by FDA. Both roles involve advocating for fairness on behalf of industry; fostering meaningful engagement with the agency; and providing information and assistance to companies in resolving specific issues and problems.

Based on my experience as the CTP Ombudsman, I can help EAS tobacco clients navigate their way through a new Center with new procedures and in compliance with a new law. Specific tobacco topics I have been involved in include: substantial equivalence, deeming (e-cigarettes, cigars, hookah), retail inspections and compliance, menthol, export/import, harmful and potentially harmful constituents, labeling, registration, standards, modified risk, adverse events, graphic health warnings, flavor ban, and user fees.

EAS clients can also benefit from my CTP and CDRH experience handling more general issues that are of concern to all industries that are regulated by FDA, not just tobacco and device companies. These included: level playing field, transparency, regulatory compliance, status of premarket and other submissions, miscommunication or lack of communication, meeting requests, difficult or unresponsive FDA employees, and of course dispute resolution. I also attended meetings between companies and FDA to ensure that they were listened to in a forum that was conducive to effective and productive dialogue.

I am available to make presentations at conventions, conferences, workshops, and other industry sponsored meetings on my new role as an EAS Senior Consultant. This is part of my outreach efforts to inform trade and professional associations and their members about what I did as an FDA Ombudsman, how I did it, and how I might now be of assistance to EAS clients and potential clients.