Medical Device Quality Auditing

Presenter: EAS Independent Consultant – George Gary Calafactor

Medical Device manufacturers understand the tight FDA regulations and legal obligations surrounding devices. From initial safety and effectiveness study design through Pre-Market Applications (PMAs), Pre-Market Notifications (PMN), registration, Good Manufacturing Practices (GMPs) through reporting of adverse events, every detail must be attended to in a thorough and documented quality system. Quality systems are key indicators of a company’s commitment to producing a safe and effective product as well as a company’s good record keeping practices as records are tested and maintained to provide transparency to FDA inspectors in the case of an audit.

The more robust the quality system the better outcome companies can expect when FDA knocks at the door for both routine audits and those which are prompted by quality questions or concerns.

Good Quality Systems are verified in a variety of ways - through in-house audits; audits with the assistance of third-party consultants who specialize in quality systems; and officially by FDA inspectors. Many companies use a combination of “mock” and “desk” audits to enhance their systems, identify gaps and initiate improved procedures where necessary.

The time to assess compliance gaps is now as a product’s quality is the basis for good business practices, ensuring the safety of customers, verifying that the product works effectively and in a manner consistent with which it was approved by FDA. Quality system audits are even used in due diligence assessments in advance of mergers and acquisitions.

Join EAS Independent Consultant, George Gary Calafactor for this EAS on-demand webinar, including detailed coverage of Medical Device Quality Auditing.

  • Learn about the types and purposes of audits
  • How FDA and EU audits differ in scope
  • How quality systems link to other systems within the business practices such as
    • Accounting and Finance
    • Purchasing
    • Customer Service
    • Marketing and Sales
    • Informational Technology
  • FDA’s enforcement requirements of quality systems (Compliance Against External Requirements and Governmental Regulations)
  • Quality Assurance (Internal Goals, Objectives, and Requirements; Continuous Improvement)
  • Quality Control (Testing and Evaluation Against Standards)
  • How FDA enforces regulations and gaps found during audits
  • Trends found in FDA enforcement for medical devices in recent years

About the Presenter:

George Gary Calafactor is an EAS Independent Consultant on matters pertaining to medical device quality assurance and regulatory compliance issues. Mr. Calafactor offers a diverse background in quality consulting, auditing, manufacturing, and pharmaceutical, biologic, and medical device operations, with vast experience in the medical device industry, internal FDA operations, and the international business arena. He performs reconciliation and FDA readiness activities associated with FDA level II QSIT inspections and revises and creates quality system procedures using FDA laws, regulations, standards, and guidance documents. He also assists in various FDA inspection backroom activities including subject matter expert coaching.

An Overview of Drug Master Files

Albert Yehaskel, Independent Advisor for Pharmaceutical Submissions

20180118

DMFs are regulatory submissions to FDA for drug substances, drug products, and/or container closures allowing FDA to review information such as confidential details about facilities, processes, components, or articles used in the manufacturing, processing, packaging, and storing of one or more APIs and/or human drugs. DMFs are at the discretion of the DMF holder and provided in the absence of relevant information in the CMC section of an application. These submissions support a third party’s application without revealing the information to the third party and maintain the confidentiality of proprietary information (e.g., a synthetic or manufacturing procedure) for the holder, allowing review of information by reviewers at FDA to support applications. The information contained in a DMF may be used to support an Investigational New Drug Application (IND), a New Drug Application (NDA/BLA), an Abbreviated New Drug Application (ANDA), another DMF, an Export Application, and any amendments and supplements to any of these applications.

Ask the Expert 2018 January

EAS is pleased to introduce a new column in our EAS-e-News called Ask the Expert. Each month our expert consultants will answer one question sent in by readers. If you’d like to submit a question, please use the Contact Us link on our website.

Allen SaylerToday’s question is answered by Allen Sayler, EAS’ Senior Director for Food Consulting Services and pertains to testing of Listeria species or monocytogenes. This question was asked at our recent webinar focusing on Listeria and the full list of questions asked by webinar participants as well as their responses are provided here.

QuestionIs it recommended to test for Listeria species or monocytogenes for all four environmental monitoring zones as well as a finished product for RTE foods?

SaylerIt is not practical or financially possible to establish a finished product testing protocol for RTE foods that is statistically valid. Therefore, a limited finished product testing program that describes taking at least one sample for each day’s production or for each production lot would provide an adequate finished product testing program. It is our opinion that for those processing environments that are associated with moist conditions or the use of water for cleaning the floors, outside of processing equipment, etc.; an environmental monitoring program should be based on detecting Listeria species, with swabbing concentrated on Zone 3 (floors, walls, door knobs, floor drains). Zone 2 should only be included if there are a positive Zone 3 swab and a vectoring strategy implemented to identify the true source. For relatively dry processing environments, it is recommended that Salmonella be the choice for detection of environmental contamination. It is strongly recommended that ATP swabbing is utilized on clean and dry FCS (Zone #1). A calibrated ATP system can provide results within 1 minute and allow the sanitation crew to reclean and re-swab the FCS to ensure it has been effectively cleaned. This approach is “preventive” versus environmental swabbing and testing of Zone #1, which can take up to 48 hours to get results as well as a similar delay it obtaining results for finished product testing for the presence of L. mono. or Salmonella. Microbial testing of Zone #1 and the finished product is “reactive”, not preventive.

EAS Webinar Replays Available for Viewing

Two new webinar replays have been added to the EAS Consulting Group website under the Events tab. We hope that you find these webinars informative. Should you have any questions, please reach out to Senior Director for Food Consulting Services, Allen Sayler.

Unraveling The Impact of FSMA On Acidified Food Regulations presented by EAS Independent Consultant and University of Vermont professor Omar Oyarzabal, Ph.D. and FDA Consumer Safety Officer Priya Rathnam.

Key Changes in SQF 8.0 presented by EAS Independent Consultant Susan Moyers, Ph.D., and SQFI Senior Technical Manager Kristie Grzywinski.

FDLI Publishes Article on The Value of FDA Pre-Submission Meetings & Enhancements under PDUFA VI Authored by EAS Regulatory Intern

The prestigious FDLI Update November/December 2017 Student Corner included an article written by EAS Regulatory Intern and recent Georgetown University graduate, Rahul. The article, The Value of FDA Pre-Submission Meetings & Enhancements under PDUFA VI, discusses how pharma companies can manage risks through proper communication with FDA throughout the drug development process.

Dynamic Year Ahead

Edward A. Steele - Chairman and Chief Executive Officer (CEO)Welcome to the January 2018 issue of EAS-e-News, our free news update for industries regulated by the Food and Drug Administration.

As with any new year, we are excited for all it will bring – anticipating new product innovation, compliance dates for regulatory requirements and expectations by the agency on matters affecting our industry.

Speaking of new product innovation, December saw a number of new efforts by the agency including a comprehensive technical framework and regulatory pathway for manufacturers of medical device products created on 3D printers. The agency has even approved its first drug which, through a porous matrix created on a 3D printer, enables patients suffering from seizures to benefit from the drugs more quickly.

This emerging technology is advancing quickly. Scientists at CDER are researching how the 3D printing of drugs impacts inactive ingredients and other drug components and engineers at CDRH are investigating the effects of design changes on safety, performance, fit and functionality. In a Guidance document released in December, FDA clarifies thoughts on 3D printing device design, testing of products and quality system requirements. This is an exciting time in the device industry and we look forward to the innovations in years to come!

Our Issue of the Month article on pharma data integrity is written by Independent Consultant, Brian Nadel. Brian discusses validation concerns and reminds us that electronic data systems must be validated at each site, using company-specific systems. He also reminds us that once FDA finds some of a company’s data to be unreliable, it considers all of the data unreliable. Stay vigilant to avoid problems down the line.

We welcome three new independent consultants – Gustavo Gonzales, Ph.D., Steve Cammarn, Ph.D. and Karen Dixon. Dr. Gonzales has a long history of assisting the food industry with safety and regulatory compliance, having held roles at Sillliker, Specialty Foods Group and Jack in the Box, and Dr. Cammarn is an expert in pharmaceuticals and personal care products with a particular focus on quality assurance of manufacturing, research and development, and Ms. Dixon is a specialist in the area of tobacco who most recently oversaw Quality Management Systems at Altria.

In addition, I would like to congratulate Cathryn Sacra who has been promoted to Director of Labeling and Cosmetics. Cathryn has been with EAS since 2008, serving in roles of increasing responsibility. She is an asset who, in her new role, will have direct oversight of projects focusing on the labeling of foods, dietary supplements, and cosmetics. I’d also like to welcome Susan Catloth who is joining EAS as the office manager.

In this issue, you will read about three expanded partnerships for EAS in the areas of SQF, pharmaceutical, and OTC regulatory training. We look forward to working with HACCP Consulting Group (SQF), CfPIE, (Pharmaceutical) and CHPA (OTC) to bring the best information on regulatory requirements to the widest audience. We look forward to seeing you at one of our upcoming seminars and webinars.

We are also introducing a new section called “Ask the Expert”. We receive numerous questions through the Contact Us link on our website, many of which we feel would be of interest to industry-at-large. In this new section, our Independent Consultants and Senior Directors will answer common questions of concern, removing any company-specific information of course. We hope you’ll find this new section to be of interest and we invite you to submit any questions that you’d like to “Ask the Expert” here.

As always, thank you for your interest in EAS and we invite you to share this newsletter with your colleagues.

Best Wishes for the Holiday Season,

Sincerely,

Ed Steele,
Chairman

EAS Webinar on the Role of Your US Agent

EAS Senior Director for Pharmaceutical and Medical Device Consulting Services, Bryan J. Coleman and Regulatory Specialist, Victoria Pankovich will co-present an EAS webinar on the Role of Your US Agent in a webinar February 27, 2018, at 10:00 am eastern.

Join us to gain a better understanding of the important basic requirements of the US Agent as well as opportunities to enhance your understanding of FDA oversight of foreign facilities.

You may register for this webinar on the Role of a US Agent by clicking here.

Cirotta to speak at Keller & Heckman Forum on e-Vapor and Tobacco

EAS President and COO, Dean Cirotta will speak at the February 6-7, 2018 Second Annual E-Vapor and Tobacco Law Symposium in Irvine, CA. This comprehensive 2-day course will address regulatory issues relevant to e-vapor, e-liquid and tobacco product manufacturers, distributors and retailers including FDA ingredient listings, premarket applications, business and IP issues, environmental issues, litigation, state laws (including Prop. 56), CPSC, EU TPD, and global regulations. Click here for more information.

Validating a Contract Laboratory – Infographic

Natural Products Insider posted an infographic on considerations for validating a contract laboratory with materials compiled from a number of 2017 Supplyside West Presentations, including that of EAS Senior Director for Dietary Supplements and Tobacco Services, Tara Lin Couch, Ph.D.

EAS Independent Consultants Offer Pharmaceutical Seminars for CfPIE

We are also pleased to announce the expansion of our regulatory training seminars in the area of pharmaceuticals through a partnership with CfPIE (the Centers for Professional Education and Excellence). CfPIE is a training company focusing on technical aspects of pharmaceutical, medical device, biotech, and cosmetics industries and EAS Independent Consultant Priya Jambhekar and independent Advisor for Pharmaceutical Submissions, Albert Yehaskel will instruct courses on Preparation of FDA Submissions and Communicating with FDA, and Stability Programs for Determining Product Shelf Life. The first offering of these courses will be held at the CfPIE headquarters in Malvern, PA in March, with additional courses to follow throughout the year in Boston, Los Angeles and Berlin. Detailed information can be found on the CfPIE webpage.

Meet Issue of the Month Author, Brian Nadel

Brian Nadel works with domestic and international clients on matters of FDA compliance and Current Good Manufacturing Practice Regulations (GMPs) as they relate to pharmaceuticals (OTC, prescription and APIs). Mr. Nadel conducts quality based audits, mock-FDA inspections and inspection readiness audits to assess site compliance with applicable requirements and assists with FDA-483/Warning Letter remediation and responses as well as general quality system CAPAs. Mr. Nadel has been a consultant since 2012, with prior careers at both FDA and industry. Mr. Nadel was the Senior Director, US Quality & Compliance and GMPs at Sanofi-Aventis, and Senior Compliance Manager, Corporate Quality & Compliance, GMP Compliance Assessment at Forest Laboratories, Inc. Mr. Nadel also worked as a compliance officer and investigator at FDA’s Center for Drug Evaluation and Research.

Pharma’s Problems with Data Integrity

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

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

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

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

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

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

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

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

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

Ask the Expert January 2018

EAS Webinar on FDA Draft Guidance: “Control of Listeria monocytogenes in Ready-To-Eat Foods: Guidance for Industry” October 31, 2017

EAS received an overwhelming response to our recent webinar on controlling Listeria monocytogenes in ready-to-eat foods. As a service to the industry, we thought it would be helpful to provide some of the questions generated by webinar participants answered by EAS Senior Director for Food Consulting Services, Allen Sayler. Please understand that these responses do not constitute consulting advice. Should you have questions or require clarification based on your own company’s situation, please reach out to Allen at asayler@easconsultinggroup.com.

Webinar Participant Questions & Answers:

  1. Can comprehensive, high sample rate finished product testing be used in place of FCS swabs? Answer: Unless the finished product testing protocol is statistically valid, it is strongly recommended that ATP swabbing is utilized on clean and dry FCS. A calibrated ATP system can provide results within 1 minute and allow the sanitation crew to reclean and re-swab the FCS to ensure it has been effectively cleaned. This approach is “preventive” versus a finished product sampling plan which is “reactive”.
  2. What do you recommend for a processing plant that produces RTE foods but during processing, there is no exposure to the environment, prior to packaging? Such as our products are in an enclosed system from Raw Material tank to Mixing tanks and to Finished Good tank. Is 21 CFR 117.130 (c)(1)(ii) fully applied?Answer: 21 CFR 117.130 (c) (1)(ii) states the following:“The hazard evaluation required by paragraph (c)(1)(i) of this section must include an evaluation of environmental pathogens whenever a ready-to-eat food is exposed to the environment prior to packaging and the packaged food does not receive a treatment or otherwise include a control measure (such as a formulation lethal to the pathogen) that would significantly minimize the pathogen.” We are of the opinion that all food processing plants, regardless of whether the product is protected from the environment prior to packaging, need some type of environmental monitoring program.
  3. Is there guidance on what “exposed to the environment” means? What about products that are processed in closed system post killing step, then packaged? Answer: The phrase “exposed to the environment” needs to be taken intuitively. However, based on the answer to #2 above, it is not necessary to “dial-in” term “exposed to the environment” as we are of the opinion every food processing plant should have an environmental monitoring program.
  4. Is the recommendation to test Listeria species or monocytogenes for all four zones and finished product testing for RTE foods? Answer: It is not practical or financially possible to establish a finished product testing protocol for RTE foods that is statistically valid. Therefore, a limited finished product testing program that describes taking at least one sample for each days’ production or for each production lot would provide an adequate finished product testing program. It is our opinion that for those processing environments that are associated with moist conditions or the use of water for cleaning the floors, outside of processing equipment, etc.; an environmental monitoring program should be based on detecting Listeria species, with swabbing concentrated on Zone 3 (floors, walls, door knobs, floor drains). Zone 2 should only be included if there is a positive Zone 3 swab and there is need to use vectoring to identify the true source. For relatively dry processing environments, it is recommended that Salmonella be the choice for detection of environmental contamination. It is strongly recommended that ATP swabbing is utilized on clean and dry FCS (Zone #1). A calibrated ATP system can provide results within 1 minute and allow the sanitation crew to reclean and re-swab the FCS to ensure it has been effectively cleaned. This approach is “preventive” versus a finished product sampling plan which is “reactive”.
  5. Is there a good number of vector sponges to take when finding a Listeria hit? Answer: The simple answer is enough to identify the true source of any positive environmental swab, particularly if the positive was found in a floor drain or on a floor source. Some industry “vectoring” plans take swabs at pre-set distances from the source in quadrants. An example might be 5 feet intervals at 0°, 90°, 180°, and 270°. These samples will provide information on the best direction to continue to gather environmental swabs to identify the true source of the environmental contamination.
  6. When an FCS is tested for Listeria, is the recommendation still that all finished product be placed on hold until a negative test result is confirmed? (For all finished product from the production run in progress when FCS testing was performed). Answer: While there is no requirement by FDA, it is common industry practice that whenever any FCS is tested for Listeria(species or monocytogenes), finished products that contain anything that came into contact with the tested FCS be put on hold until such time as the results of the swabbing are known. If such product were to be released to customers or consumers and the FCS swabbing came back positive for Listeria, then an immediate Class I recall with a public press release would be the likely outcome. Utilizing ATP swabbing technology is a much more effective way to routinely detect and correct unclean FCS.
  7. What would you recommend that facilities producing RTE products with a short shelf life (produce, packaged salad kits, etc.) approach Zone 1 testing?Answer: See the answers to #1, #4 & #6. It is our opinion that there should be no direct environmental swabbing of Zone 1 for Listeria or any other human pathogen. ATP technologies work much better and provide an almost immediate feedback so the unclean FCS can be recleaned and sanitized prior to any contact with food ingredients, food packaging or the food itself.
  8. Do these new guidelines apply to frozen vegetables? Answer: In Section III of the draft Guidance document, any process (freezing) needs to be validated to determine whether there is a listeristatic or listericidal effect that will demonstrate that the food is not adulterated. While frozen vegetables originate from fresh produce covered by the FDA FSMA Produce Safety regulation, microbiologically, the Listeria bacteria is not killed by freezing but does not reproduce (listeristatic). Once frozen vegetables contaminated with Listeria is thawed, Listeria starts to grow and become a human health threat so yes, the FDA draft Guidance would also apply to frozen vegetables. On page 32 of the draft guidance, it states the following, “Many foods are stored in a frozen state – e.g., to extend shelf life before retail sale or as a product available to consumers in the frozen state. L. monocytogenes does not grow at temperatures below freezing (Ref. 12 and Ref. 13). Therefore, freezing is a particularly effective temperature control measure to prevent growth during storage. Freezing will not eliminate L. monocytogenes from foods and cannot be relied upon as a control measure for the elimination or reduction of Listeria monocytogenes.”
  9. How does FDA define finding Listeria spp or L. mono. “on occasion?” In other words, what is “too high” a rate of detection. Answer: We are not aware of any FDA-based numerical definition of finding Listeria “on occasion”, or what is “too high” a rate of detection of Listeria in environmental swabs. Of much more importance to FDA and to customers and consumers in general, is the corrective action follow-up and root cause analysis conducted to identify the true cause of the positive Listeria swab and adjust manufacturing operations to eliminate the real source of the contamination.
  10. What is the FDA expectation of Listeria levels in a plant? Answer: We are not aware of any FDA-based numerical expectation of what might be an “acceptable” number of Listeria swabs being positive versus negative. What is of more importance is the frequency of re-occurrence and response to positive samples. If the same swabbing location was positive for Listeria every other month for 6 months, then that indicates a failure to identify the true root cause. We are aware of an unpublished and non-scientific practice where more than 3 positive in 100 samples, regardless of location, may indicate a more thorough corrective action effort is needed. It is very important that all environmental monitoring results be incorporated into some type of trend analysis to determine if patterns of positive results exist that need additional attention.
  11. How does the FDA Draft Lm Guidance relate to the FDA Food Code and application in the retail grocery environment? Answer: All FDA guidance documents represent FDA’s current thinking on a topic. Many times, this guidance is intended to clarify the section of an FDA law or regulation. The draft guidance specifically states that it is not intended to be applicable to retail food operations. The Retail Food Code (applicable to grocery stores and restaurants) is utilized by FDA to provide the requirements for retail food operations. It is essentially a Public Health Code or model, not an FDA law or regulation, intended for adoption by states, counties and local governments. Modification of the Retail Food Code must be done through submittal of proposals to the Conference on Food Protection, which meets approximately once every two (2) years to consider new proposals.
  12. What is the FDA perspective on the risk associated with finding L. monocytogenes in the environment in raw vs. RTE areas? Answer: We are of the opinion that FDA is utilizing a positive environmental swab result for L. monocytogenes in “raw” areas of the processing facility as evidence that this source could find its way into the RTE areas of the processing operations. They are very likely to intensify their efforts to identify L. monocytogenes in RTE areas. If none is found, FDA is likely at a minimum to note the positive L. monocytogenes result in their Form FDA 483 observations.
  13. Is FDA focusing in finding Listeria in raw areas, while using Whole Genome Sequencing, even if processing facilities have implemented adequate raw-RTE separation and controls? Answer: FDA is utilizing pulsed-field gel electrophoresis (PFGE), multiple locus variable number tandem repeat analysis (MLVA), and whole genome sequencing (WGS) as the main tools for the PulseNet’s fingerprinting of food pathogens. It is our understanding that all positive environmental swabs that detect a foodborne human pathogen are analyzed using PFGE at a minimum, regardless of the location of the swabbing.
  14. Does the guidance doc require zone 1 sampling 3-4 hours into production? Or is that for zone 2 and 3? If it is zone 1, what kind of swabbing is required? Listeria spp? or L. mono.? Answer: An FDA Guidance document cannot “require” anything, but as stated in the answer to #11 above, it is the Agency’s most current views. FDA field investigators are not authorized to enforce any FDA Guidance documents but can use the information in such document as a benchmark to measure whether the industry is taking reasonable precautions to ensure their food is safe. On page 37 of the draft guidance, there is a reference to taking environmental samples 3 – 4 hours after the start of production. On page 36 of the draft guidance, it states, “We recommend that even the smallest processors collect samples from at least 5 sites of FCS and 5 sites of non-FCS on each production line for RTE foods. We recommend that larger processors determine the appropriate number of sampling sites based on the size of the plant.”It is our opinion based on answers to previous questions, that any environmental swabbing is conducted primarily on Zones 3 for the detection of Listeria species. This is not the recommendations from FDA found in the draft Guidance document, which states on page 37,
    • Collect environmental samples from specific FCSs on the production lines at least once every week when the plant is in operation; and
    • Test each FCS in the plant at least once each month.
  15. Does the recommendation to test Zone 1 for Listeria apply to high-risk foods only? Do you expect Zone 1 to be tested in low moisture/Aw food plants? Answer: Based on the current statements in the draft Guidance, FDA appears to be making no differentiation between low-risk, medium-risk and high-risk foods regarding the recommendation to gather environmental swabs for FCS (Zone 1).
  16. What is more powerful? Testing finished product based on ICMSF N=20 or more samples or zone 1 testing (but not test finished products)?Answer: A Zone 1 (FCS) positive test for L. monocytogenes should be considered the same as a positive finished product test. It is our opinion that the preferred testing program for RTE food manufacturers focuses on environmental testing as a means to implement preventive controls rather than finished product testing, which is a reactive approach. Sampling should consist of:
    • A credible number of environmental swabs taken primarily in Zone 3, and
    • Effective corrective actions including additional environmental samples and vectoring for any positive environmental samples, and
    • Utilization of ATP swabbing at every production start-up on a representative number of FCS and immediate recleaning if the calibrated ATP result is “positive”, and
    • Accumulating a set of retailed finished product samples (one from each production lot) and storing these to the end of the shelf life of the finished product, and
    • Test a minimum number of finished product samples (one per production run or production day) for foodborne pathogens, which for most foods would be L. monocytogenes and for dry foods, Salmonella.

EAS Partners with HACCP Consulting Group on SQF 8.0 Seminars

EAS Consulting Group is pleased to partner with HACCP Consulting Group, a Safe Quality Foods Institute (SQFI) Training Center, for training programs aligned with the SQF Code, edition 8.

The next seminar in Chinese Camp, CA, February 6-7, 2018 followed by Dayton, OH, February 26-27, 2018 is on Developing and Implementing SQF Systems. This course provides instruction, examples, exercises, and tools necessary for successfully implementing an SQF System. This is one step in the qualification process for SQF Practitioners and an excellent choice for all food safety team members.

Produce Safety Requirements for Large Firms

The coming year will be a busy one for food firms as the compliance date for 14 components of the FSMA Final Rule come into effect. FDA has published a helpful tool, Key Dates for Compliance, which runs through 2024 and this quick, color-coded reference offers a handy visual for determining when the compliance date for each area of FSMA goes into effect.

Of particular note is the compliance date of January 26, 2018 for the Produce Safety Requirement for large firms, (except certain water requirements) which applies to growers of fruits and vegetables that are consumed raw, with a few exclusions – specific types of produce that are rarely consumed raw (such as asparagus, coffee beans and pumpkins); those which would undergo further processing reducing the likelihood of contamination by microorganisms that could harm public health; produce which is grown for personal use; farms which have a three year annual sales totaling less than $25,000 and produce which is not a RAC.

A brief review of the water requirements makes clear why the agency is taking more time to find a way to protect consumers that is also practical and efficient for producers. Right now, the Produce Safety requirements and benchmarks for water testing are designed to be flexible, depending on the agricultural use and whether the water is received from municipal sources or other systems that have acceptable established standards, such as valid certificates of compliance that the water meets relevant requirements, or if the water is treated in compliance with the rule. Its very flexibility is leaving many producers wondering what would work best, if at all, in their own particular case.

Agricultural water is estimated to be the most significant pathway of E. coli contamination. So, it is unacceptable for water used in hand washing during and after harvest, water used on food contact surfaces, that comes in direct contact with produce (including ice) during or after harvest, or that is used for sprout irrigation to have any trace of E. coli.

Untreated surface water that is directly applied to growing produce (other than spouts) is considered to be the most vulnerable to external influences. FDA requires farms to do an initial survey, using a minimum of 20 samples, collected as close as is practicable to harvest over the course of two to four years. After that, an annual survey of a minimum of five samples per year is required. Those five newest samples in combination with 15 of the most recent samples will create a “rolling dataset” of 20 samples for use in confirming the safety of the water in use.

For untreated groundwater that is directly applied to growing produce (excluding sprouts) farms must take a minimum of four samples, again collected as close as is practicable to harvest, during the growing season or over a period of one year. After that, a minimum of one sample should be taken annually and that latest sample, combined with three of the previous samples will create the rolling dataset of four samples confirming that the water is appropriate for use.

The water’s safety is calculated using these samples through a complex statistical process with two sets of criteria for microbial water quality called the geometric mean (the average amount of generic E. coli in a water source) and statistical threshold (the amount of variability in the water quality). The sample’s generic mean must be 126 or less CFU of generic E. coli per 100 mL of water and the statistical threshold must be 410 CFU or less of generic E. coli in 100 mL of water. The determination of these statistical analyses may be confusing and FDA is considering the creation of a usable online tool to help make sense of individual data.

In the many US produce growing areas, the only available water for irrigation is untreated surface water that does not and cannot practically be treated to meet the microbiological criteria in the current rule. There is scant evidence of harm to consumers from the use of these water sources in some areas. At the same time, there is ample evidence of the risk that untreated surface water does cause illnesses in human. FDA is taking more time to sort out why what seems to be equally unacceptable agricultural water does cause illness in some situations but not in others.

There are numerous other components to the Produce Safety Rule such as a Biological Soil Amendment, which is somewhat in flux as the agency continues to assess the number of days needed between the applications of raw manure as a soil amendment and crop harvesting in an effort to minimize the risk of contamination. Currently, FDA thinking states that untreated biological soil amendments of animal origin must be applied in a manner so that it does not contact covered produce during application and minimizes the potential for contact with covered produce after application. FDA also feels that the USDA’s National Organic Program standards, which call for a 120-day interval between the application of raw manure for crops in contact with the soil and 90 days for crops not in contact with the soil to be a prudent approach while it continues its own risk assessment.

There is also a provision for working and grazing animals, whereby farmers that allow animal grazing on land where produce is also grown should take every reasonable step to not harvest produce that is likely to be contaminated and should consider (but are not required) to implement waiting periods between grazing and harvesting.

Workers and visitors to the farm or facilities must be educated on and use good hygiene practices such as washing hands, and workers who handle covered produce and food contact substances must have must have training, education, and experience to perform their responsibilities and have adequate tools, equipment and buildings to do so in a manner that prevents contamination such as appropriate storage, maintenance, clean equipment, and tools.

Lastly, sprouts have received much attention as they are particularly susceptible to microbes causing foodborne illness and there are numerous testing requirements under the Produce Safety Requirement, many of which pertain to water usage. Among other requirements, farms must test spent sprout irrigation water from each production batch or in-process sprouts for certain pathogens. In addition, sprouts cannot be allowed to enter commerce until these pathogen test results are confirmed to be negative.

In an agency Q&A on Water Safety Requirements it was noted that the Produce Safety Requirement is anticipated to bring about a reduction of over 60 percent in the risk of contamination from agricultural water, and a reduction of about 20 percent in the total number of foodborne illnesses associated with produce with an expected overall reduction in costs related to foodborne illnesses of $477 million.

What does all this mean? For one, FDA now has enforceable regulations for both domestic and international produce growers for the safe growing, harvesting, packing and holding of fresh produce. The specific requirements with regards to water testing leave no room for interpretation as to what constitutes a safe supply and FDA will request access to that data history for their own assessments of safety. As with any compliance requirement, accurate and complete documentation is necessary to satisfy FDA requirements. Under § 112.161(a)(1), all records required must include, as applicable, the name and farm location, actual values, and observations obtained during monitoring, an adequate description of covered produce applicable to the record, the location of the growing area or other areas applicable to the record, and the date and time of the activity documented, signed and dated. These records must be kept in a safe location, whether electronic or paper storage for a period of time. That time, however, is currently undetermined as FDA has not yet addressed issues related to traceability and additional record keeping of high-risk foods as mandated under FSMA section 204.

Visit FDA’s FSMA Final Rule on Produce Safety for more details on the components of the Produce Safety Rule including Draft Guidance for Industry for the Compliance with and Recommendations for Implementation of the Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption of Sprout Operations.

After January, the next FSMA compliance date will be March 19, 2018, with new requirements for importers of human and animal foods. Stay tuned…

EAS Welcomes Three New Independent Consultants

Stephen R. Cammarn, Ph.D.

Stephen Cammarn is an expert in pharmaceuticals and personal care products with a particular focus on quality assurance of manufacturing, research and development. Prior to consulting Dr. Cammarn built a career at The Procter & Gamble Company where he oversaw quality assurance and quality control in plants across six continents and had direct oversight in areas such as formulation, process engineering, and technical services. Dr. Cammarn’s doctorate is in Pharmaceutical Science from The University of Cincinnati and his bachelors are in Chemical Engineering from Ohio State University.

Karen Dixon

Karen Dixon consults in the area of tobacco. She has a strong focus on the development and implementation of FDA readiness programs including processes, compliance considerations and integration within all levels of an organization (Regulatory Affairs, Quality System, OSHA, ISO, Sarbanes-Oxley). Her unique combination of expertise in operations, training systems, finance, product quality, Quality Management Systems, regulatory affairs, and ISO-9001-2015 makes her a valuable asset to EAS clients. Karen has held positions such as Manager, Quality Management System at Altria and Philip Morris USA. She has an MBA from Montreat College in North Carolina and is a Certified Quality Auditor (CQA) with the American Society for Quality.

Gustavo Gonzales, Ph.D.

Dr. Gonzales has a long history of regulatory compliance strategic planning. He is an expert in food safety and quality with a particular expertise in meat sciences and has a 24-year track record of implementing policies and procedures that align with industry R&D trends and best practices at companies such as Jack in the Box and Specialty Foods Group. Dr. Gonzales works in a variety of food sectors on programs such as allergen control/prevention, auditing functions, distribution systems, environmental monitoring, FSMA, GFSI, retail operations, and sanitation. He has a Ph.D. in Meat Science from Iowa State University with certifications as a Food Safety Manager, International Dairy Foods Association HACCP, and is a Lead Instructor for FSPCA Preventive Controls for Human Foods.

EAS Partners with CHPA OTC Academy for Webinar Series

EAS is pleased to partner with the Consumer Healthcare Products Association (CHPA) starting in January 2018 for a five-part webinar series focusing on a number of topics of interest to the industry. EAS Independent Consultants will present topics on Managing Foreign FDA Inspections, Adverse Events Reporting, Conducting a Scientifically Sound OOS Investigation, Managing Domestic FDA Inspections and Responding to 483s and Warning Letters, all of which are open to CHPA members and non-members.

January’s webinar on Managing Foreign FDA Inspections is presented by Peter Saxon. He’ll discuss regulatory problems often found in FDA inspections, how OAI (Official Action Indicated) results are categorized by the FDA and the ensuing consequences, and on-going steps companies can take in an effort to maintain good oversight of facilities.

Cathryn Sacra Promoted to Director, Labeling and Cosmetics

Cathryn SacraEAS clients who need assistance in the area of labeling and cosmetics are well familiar with Cathryn Sacra, who was recently promoted to Director of Labeling and Cosmetics. Cathryn has been with EAS since 2008, serving in positions of increasing responsibility. She holds an undergraduate degree from Harvard University.

Susan Catloth Joins EAS as New Office Manager

Susan Catloth recently joined EAS as office manager. Susan brings a wealth of organizational and skills and experience to the team and will assist with various projects as well as provide front-line communication and service for those contacting EAS home office. Prior to EAS, she worked at the Motley Fool where she held the positions of Project Manager, Investing Team, and Video Operations Manager. Susan’s skills in video and content production will enable EAS to expand our digital training platforms.

December 2017 FDA Drug / Medical Device Activity

We would like to highlight one of the Draft Guidance issued by the FDA this month.**The U.S. Food and Drug Administration proposed a new, risk-based enforcement approach to drug products labeled as homeopathic. This proposed new approach would update the FDA’s existing policy to better address situations where homeopathic treatments are being marketed for serious diseases and/or conditions but where the products have not been shown to offer clinical benefits. It also covers situations where products labeled as homeopathic contain potentially harmful ingredients or do not meet current good manufacturing practices. Under the law, homeopathic drug products are subject to the same requirements related to approval, adulteration and misbranding as any other drug product.

With the new drug listing regulation, all companies have been given a renewed opportunity to ensure their listings are complete and accurate. This includes the label uploaded to the drug listing. The FDA recently issued a warning letter to a company whose listing did not match the product in commercial distribution. Do keep in mind that the FDA requires all changes to a drug listing to be reported as soon as possible but no later than the June or December following the change. As of FDA FY 2018, all drug listings must be certified as accurate by 31 December of each year. Any listing that has not been updated or certified as accurate according to the regulation will be considered expired by the FDA in January of the following year.

Guidance Document updates on the FDA website:

CDER:

CDHR:

CBER:

CDRH and CBER: