GMPs for OTCs – Improving Compliance as FDA Eyes Enforcement Actions

Presented by Bryan Coleman, EAS Senior Director for Drugs and Medical Devices

With more than 80 therapeutic categories, Over-the-Counter (OTC) drug products play an ever-increasing role in health care. FDA’s Center for Drug Evaluation and Research (CDER) working in conjunction with the Office of Regulatory Affairs (ORA) ensures that OTC products are safe to use, appropriately labeled, adverse events reports are filed and that all products are manufactured under the appropriate quality control measures. Generally, the FDA’s first and best opportunity to assess the quality and compliance conformance of an OTC drug will be during an on-site inspection of the manufacturing facility. From a Good Manufacturing Practices (GMP) perspective, manufacturers must recognize that the FDA applies the same, stringent 21 CFR 210 and 211 drug GMP standards to OTC products just as prescription drugs are held to. Thus, OTC drug manufacturers (and contract manufacturers) must maintain vigilance at all times with all aspects of production quality and documentations. From the physical plant and grounds, employee training, testing and specifications, including Out of Specifications (OOS) results management, compliance expectations with 21 CFR 211 are clearly articulated.

About the Presenter

Bryan Coleman

Bryan Coleman

Join Bryan Coleman, EAS Senior Director for Drugs and Medical Devices for a complimentary webinar on June 13, 2019 at 1:00 pm eastern where he will discuss the specifics of GMP compliance under 21 CFR Part 211 and common pitfalls that warrant increased FDA attention.

Understanding the Food Fraud Puzzle

EAS, SQFI and Food Safety News Offer a Complimentary Webinar

EAS Consulting Group
SQF Institute
Food Safety News

With long supply chains that can stretch around the world, Food Fraud is a hot topic for the food industry, consumers and government regulators. Food fraud’s negative impacts cause financial harm to the food manufacturing industry and public harm while fostering consumer mistrust. Examples of food fraud can be found in many food sectors including spices, seafood, meat and dairy as well as more specific examples such as olive oil, honey, coffee and saffron, just a few.

Substituting cheap ingredients and food additives is called “economic adulteration”, a violation of US federal law. In addition, when dangerous ingredients are used, crossing the line into “intentional adulteration” the crime is a felony, with the potential for jail time.

Learn what tools are available to food manufacturers and government regulators to combat this growing problem. Novel application of next-generation sequencing (NGS) screening and identification of multispecies which aims to improve food authenticity and tackle food fraud will be discussed.

How can you confirm suspicions of food fraud in order to avoid being a victim? What can you do to protect against food fraud and how can you ensure your products have all the safety nets in place to defend against intentional adulteration?

This webinar will provide a background on food fraud and provide an overview of tools available to meet the challenge of economic loss and consumer illness, injury or death caused by those with s nefarious, and potentially deadly, criminal intent.

Join Mehrdad Tajkarimi, Ph.D., EAS Independent Consultant and Leann Chuboff, VP of Technical Affairs at the Safe Quality Foods Institute (SQFI), co-sponsored by Food Safety News, for a webinar covering the many facets of food fraud and food defense and some of the mitigation strategies that must be put in place for prevention. Learn real world perspectives, definitions and solutions on a micro and macro level.

About the Presenters

Mehrdad Tajkarimi, Ph.D.

EAS independent consultant, Mehrdad Tajkarimi, is an expert in national and international food safety regulations, warehouse and wholesale manufacturing, dairy, grain, poultry and retail industries, HACCP, food defense, ISO 22000, BRC. He assists clients with organic requirements, Food Safety Modernization Act (FSMA), as well as in natural food preservatives and packaging, foodborne pathogenic and spoilage microorganisms characteristics, SPC and shelf life studies.

Leann Chuboff

LeAnn Chuboff has over 30 years of foodservice experience specializing in supply chain food safety and quality assurance. Currently LeAnn is the Vice President of Technical Affairs for the Safe Quality Food (SQF) Institute responsible for the technical elements of the SQF program including the development, maintenance and technical support of the SQF Code and supporting materials. Prior to working at the SQF Institute, LeAnn worked for the National Restaurant Association Solutions as the Director of Science and Regulatory Relations. In this role, she was responsible for the technical accuracy of the ServSafe food safety program and developed program and services on food safety and food defense to fit with all segments of the restaurant industry. LeAnn has also worked for Long John Silver’s and Boston Market in corporate quality assurance where she developed food safety and vendor approval program. LeAnn graduated from Iowa State University with a B.S. in Food Science and is active with many organizations including GFSI, AFDO and the International Association for Food Protection. She sits on several committees in an effort to enhance policy and develop programs for the industry to help protect public health.

About EAS Consulting Group

EAS Consulting Group continues 55 plus years of leadership in providing regulatory consulting to the industries regulated by FDA and other federal and state agencies. Our network of independent advisors and consultants enables EAS to provide comprehensive consulting, training and auditing services to the dietary supplement, pharmaceutical, food, medical device, tobacco and cosmetic industries. Whether the need is assistance with general FDA or USDA regulatory compliance or more specific needs such as product development, New Dietary Ingredient submissions, FSMA regulation compliance, generic or customized compliance trainings, 483 responses, product market withdrawals or recalls, mock-FDA audits, expert witness services, GRAS & food additive issues, dietary supplement labeling compliance or the development of a detailed import strategy and policy, EAS, with its over 150 consultants, former FDA compliance officials and industry experts, is able to assist. With vast expertise in FDA’s policies and enforcement, EAS is the proven choice for assistance in FDA and other regulatory matters.

About Safe Quality Food Institute

The Safe Quality Food (SQF) program is recognized by retailers and foodservice providers around the world as a rigorous, credible food safety management system. It is the only certification system recognized by the Global Food Safety Initiative (GFSI) that offers certificates for primary production, food manufacturing, food packaging, distribution and retail/wholesale grocers. This enables suppliers to assure their customers that food has been produced, processed, prepared and handled according to the highest possible standards, at all levels of the supply chain. Additionally as a division of the Food Marketing Institute (FMI), the SQF program incorporates continual retailer feedback about consumer concerns. This information is passed on to SQF certified suppliers, keeping them a step ahead of their competitors.

About Food Safety News

Food Safety News pulls together a team of talented journalists to provide timely reporting on food safety issues. Our original, in-depth reports are published daily, and are complemented by contributed articles and opinion pieces written by food safety leaders from every sector of the industry. Our reporters have been granted access to the White House, the Supreme Court, and multiple Congressional offices alongside the nation’s leading newspapers and media networks and provide outstanding, award-winning coverage of topics ranging from policy and politics to foodborne illness outbreaks to sustainability, science and research.

Join EAS for Complimentary Webinars

EAS will host two complimentary webinars in June. First, on the 18th, EAS Independent Consultant Mehrdad Tajkarimi, Ph.D. teams up with Leann Chuboff from SQFI for a webinar on understanding the food fraud puzzle. This webinar is co-sponsored by Food Safety News magazine and will be held at 1pm eastern. Register here.

On June 20, also at 1pm eastern, Senior Director for Pharmaceuticals and Devices, Bryan J. Coleman, will present on GMPs for OTCs with suggestions for how to improve compliance as FDA ramps up enforcement and inspections. With more than 80 therapeutic categories, OTC drug products play an ever-increasing role in health care and manufacturers must recognize that the FDA applies the same, stringent 21 CFR 210 and 211 drug GMP standards to OTC products. Register for the GMPs for OTCs webinar here.

Challenges with Implementing Cleaning Validation

By Miguel Montalvo

Though published well over 25 years ago, FDA’s guidance surrounding cleaning validation continues to cause industry confusion. While everyone agrees that cleaning validation is critical, the application of incorrect or ineffective approaches whether by misunderstanding the purpose of validating cleaning procedures or taking an extremely conservative approach create impractical demands on resources.

Planning is the root of all successful and compliant cleaning validation programs to ensure the assessment will accurately test the desired points. These plans will include a process flow to determine the activities to be conducted starting with the development of matrices for equipment/cleaning procedure combinations for all manufactured products. The next step is to select a worst-case product for each equipment/cleaning procedure combination. It is acceptable to use product family grouping if applicable. Once the worst-case product(s) is(are) chosen, analytical methods that quantify residue levels of target components of these product must be established, including acceptable limits for the residues (also called Maximum Carryover or MACO). The CV protocol can also be prepared at this point. Also, as part of the planning stage, a review of all training programs and process for the cleaning procedures will help to ensure adequate levels of challenges and qualifications are incorporated.

Prerequisites within each protocol execution must be established before initiating cleaning validations. This includes equipment design, analytical methods, adequate cleaning procedures, employee training and calibration of equipment. Cleaning procedures appropriate to each piece of equipment must be documented in appropriate detail. It is not always necessary for the analytical methods to be specific to the chemical entity under examination. If a non-specific method that appropriately measures and quantifies residues of interest under the sampling conditions applied, it’s use may be appropriate. Non-specific analytical methods save time by a considerable factor.

It should be noted that cleaning and sanitizing are often incorrectly combined into one step. The reason these should not be combined is the differences in the purposes. Cleaning is concerned with removing the residues from the previous product (and the cleaning agent if applicable) using a worst-case dirty hold time. Sanitization is concerned with the condition of the equipment before it is used next, particularly from a microbial consideration. As a good option, many companies are establishing a sanitization process/step before using the equipment again and this step is validated separately from the cleaning validation. Or, separately they may test for the microbial bioburden in the equipment surface after the worst-case clean hold time has elapsed to see whether a sanitization step is necessary. If the test fails, the option will be to apply a sanitization step which could be as simple as a high purity water rinse or other more sophisticated processes such as a hydrogen peroxide rinse/application. Of course, these considerations will be affected by the type of product/process being manufactured – from a topical drug, oral solid dosage to the more critical sterile products, specifically those aseptically filled.

There are many considerations when designing and implementing a cleaning validation approach. Ensuring due diligence is paid to assessing and determining which factors best suit each situation will pay dividends in the long run with a thorough and well documented program.

For more information on cleaning validation, including critical missteps, you may wish to view Miguel’s full length article recently published by the International Society of Pharmaceutical Engineers blog (ISPE iSpeak). EAS offers assessment and development of cleaning validation protocols. Contact us to learn more.

EAS Offers Pre-Clinical Safety/Tox Study Services for GRAS and NDI Submissions.

EAS offers holistic and cohesive services for clients looking to submit GRAS and NDI submissions to FDA. From the assessments to design of early feasibility studies, ongoing study oversight with the Contract Research Organization, strategy meetings with FDA and the preparation and dossier submissions, EAS’ expert toxicologists, microbiologists and chemists work closely to ensure prioritization of your study needs and execution. 

Choose EAS for:

  • Determination of required performance outcomes and appropriate studies 
  • Development of study design and protocols
  • Identification of an appropriate Contract Research Organization (CRO)
  • Coordination of the study initiation and management oversight with the CRO
  • On-going monitoring of study protocols and outcomes
  • Input of appropriate data for inclusion in study reports
  • Support the writing of the dossier for FDA submission

What are the Steps to Reporting an Adverse Event to FDA?

By Robert Fish

Each month EAS independent consultants answer one question sent in by readers of EASeNews. This month’s question on adverse events reporting for both OTCs and dietary supplements is answered by Independent Advisor for Quality and Compliance, Robert Fish. Mr. Fish spent 33 years with FDA, including time as the Director, Division of Field Investigations where was responsible for general policy and guidance for the Agency’s domestic and international investigation activities. He has expertise in compliance matters and cGMPs as they relate to pharmaceutical, device, and biologics manufacture. Further, Mr. Fish is ISO 9000 Lead Assessor Trained and is an AFDO Certified HACCP Instructor. He is a sought-after expert, speaking at international events on FDA inspections and GMPs.

Question: What are the steps to reporting an Adverse Event to FDA? 

Fish: In December 2007 the Dietary Supplement and Non-prescription Drug Consumer Protection Act (The Act) became effective. That law required that all over the counter drug and dietary supplement manufacturers and distributors investigate and report to FDA any serious adverse event reports concerning any of their marketed products.

The Act defines an adverse event as any undesirable experience associated with the use of a medical product in a patient. The event is considered serious when the patent outcome is:

  • Death
  • Life-threatening
  • Hospitalization (initial or prolonged)
  • Disability or Permanent Damage
  • Congenital anomaly/birth defect

Other serious (example-required medical or surgical intervention, allergic bronchospasm)

The Act requires that reports of serious adverse events be reported to FDA within 15 business days of receiving the information. The reports are required to submitted using Med Watch Form 3500A.

FDA issued Guidance for Industry concerning this adverse event reporting as well as guidance for completion of the Med Watch 3500A form.

Companies must have procedures in place to screen all complaints for any possible indications of adverse events with the marketed products. Those that meet the definition of serious must be investigated and reported on the Med Watch Form 3500A within 15 business days. Screening of the complaints may require the assistance of medically trained staff.

Once a 3500A has been submitted, update reports can and should be submitted as more information becomes available. 

EAS offers assistance with the completion of 3500A reports as well as assessments of consumer comments and complaints for applicability to this regulation. Contact EAS for more information.

Couch to Speak at the ACI – CRN Legal, Regulatory and Compliance Forum

Tara Couch will also speak at the ACI – CRN Dietary Supplement Legal, Regulatory and Compliance Forum taking place June 18-20, 2019 in New York City. Tara will present as part of a panel called Coattails, Master Files, and NDIs which will be held on June 18 and will be analyzing the latest statements and activities from FDA with regard to NDI systems and guidance that would help protect the manufacturers’ significant investment in developing new dietary ingredients; comparing similarities with FDA’s proposals for NDIs to similar proprietary systems enforced by FDA; and exploring mechanisms for FDA enforcement.

Final Guidance for Food Contact Notifications – Infant Formula and / or Human Milk

FDA’s Final Guidance for preparation of Food Contact Notifications for substances that come into contact with infant formula and human milk is intended to help industry understand FDA’s process for evaluating the safety of food contact substances. It incorporates the latest scientific thinking about the effects chemical substances may have on infant health. If you missed the recent EAS webinar on infant formula submissions, you may find it On-Demand. If you have specific questions about this Guidance, development of infant formula products, including GRAS submissions, or submission of a Food Contact Notification contact EAS.

EAS Exhibiting at Future Food Tech

EAS Senior Director for Food Consulting Services, Allen Sayler and Independent Consultant, Ron Levine, will represent EAS at Future Food Tech – NYC taking place June 18-19, 2019 in New York City. Stop by the EAS booth to learn more about our services for food innovators such as product development and labeling, food additive submissions for new ingredients, claims substantiation and more.

Challenges with Implementing Pharma Cleaning Validation

Edward A. Steele

Dear Reader,

Welcome to the June 2019 issue of EASeNews, the free newsletter for FDA regulated industries. FDA has been busy with initiatives this month. As you’ll see in our What’s New at FDA section, two of these include FDA’s finalized Guidance for abbreviated drug submissions as well as food contact notifications products that come into contact with infant formula and human milk. Additionally, FDA announced the decision to extend the registration period for the Voluntary Qualified Importer Program (VQIP) for fiscal year 2020 until July 31, 2019. Annual benefits will then take effect beginning October 1. VQIP is a voluntary fee-based program established by the FDA FSMA that provides for expedited review and importation of human and animal foods into the US for approved applicants who achieve and maintain a high level of control over the safety and security of their supply chains. If you feel your company qualifies for VQIP or would like an assessment or assistance completing the application process, please feel free to contact me.

I am happy to say EAS has announced our fall line-up of compliance seminars taking place in Irvine, CA. We are offering Dietary Supplement Labeling November 12-13, 2019 Food Labeling November 14-15 and Dietary Supplement GMPs November 14-15. We invite you to register now for early-bird pricing.

We welcome two new consultants this month, Tom Jonaitis and Veronica Ortiz de Montellano, both of whom will be of invaluable assistance particularly to clients working with both USFDA and Health Canada as well as firms operating in Mexico who export products to the US.

Our issue of the month is written by Miguel Montalvo and discusses some of the many challenges with pharmaceutical Cleaning Validation. This article is a condensed version of a full-length feature published by the International Society of Pharmaceutical Engineering’s website, ISPE iSpeak. EAS consultants are pleased to provide monthly articles for ISPE iSpeak readers on a variety of topics pertaining to the pharmaceutical and OTC-drug industry. Our Ask the Expert is written by Robert Fish, Independent Advisor for Quality and Compliance and discusses Adverse Events Reporting requirements; and our Did you Know covers EAS capabilities with Contract Research Organizations (CROs) which are heavily utilized and a lifeblood for companies conducting safety studies in the preparation of food additive submissions.

We have two complimentary webinars coming up in June – on June 18 independent consultant Mehrdad Tajkarimi, PH.D. and Leann Chuboff of SQFI will discuss the food fraud puzzle. This webinar is co-sponsored by Food Safety News magazine. On June 20 Bryan J. Coleman, Senior Director for Drugs and Devices will present on GMPs for OTCs and how to improve compliance. We hope that you join us for these and watch any of our previous webinars available on-demand on the EAS website, including May’s webinars on cosmetics claims and how FDA views certain terms when considering whether a product to be a cosmetic or unapproved new drug; and compliance with 21 CFR Part 11.

Thank you as always for your interest in EAS and please feel free to share this newsletter with your colleagues.


Edward A. Steele Signature

Edward A. Steele

Fairman Authors Supply Chain Transparency and Quality Assurance Articles for Natural Products Insider

EAS Independent Consultant Heather Fairman authored two recent articles for Natural Products Insider. First, Supply Chain Transparency on the demand by consumers and regulators for supply chain transparency from farm to fork. Next, Quality Assurance for manufacturers of nutrition bars. In addition to consulting for EAS, Heather is a technical advisor for the Small Island Developing States (SIDS) DOCK Island Women Open Network (IWON,, an intergovernmental organization.

Cathey on Creating Dietary Supplement Specifications

Tamika Cathey was a guest columnist for Ask the Expert in Tablets and Capsules Solid Dose Digest where she responded to the question of creating a dietary supplement specification program that meets FDA expectations. In June 2007, the FDA published 21 CFR Part 111, which established cGMP requirements for dietary supplements. Since then, manufacturers have struggled to understand and comply with these requirements regarding specifications development.

Meet June 2019 Issue of the Month Author Miguel Montalvo

EAS Consulting Group independent consultant, Miguel Montalvo, is an expert in GMP and GAP assessments for pharmaceuticals, including injectables, solid dosage, OTC topicals and biologics, as well as medical devices and dietary supplements. He has developed, implemented, reviewed, managed and audited quality and GMP compliance functional procedures including those related to laboratory operations, Quality Systems, CAPA, Non-Conformance documentation, Change Control management, calibrations, procedural and documentation controls and internal audit programs. Prior to consulting Miguel worked in industry holding positions at Baxter Healthcare and Bristol Myers Squibb.

Meet New Consultants for June 2019

Tom Jonaitis

Tom Jonaitis

Canadian-based Tom Jonaitis works with clients in the food, dietary supplement, consumer product and related industries, providing comprehensive toxicology and regulatory consulting guidance and support. He is an expert in regulatory evaluations including scientific literature hazard reviews and summaries, as well as creating pre-market quality and safety dossiers for novel food and dietary supplement ingredients applications to government agencies – FDA, Health Canada and Australia’s TGA, FSANZ. Tom reviews and evaluates the results of in vitro and in vivo toxicological studies and has additional expertise in pesticide/agricultural chemical regulations, workplace hazard classifications, and spray foam human health risk assessments.

Veronica Ortiz de Montellano

Veronica Montellano

Veronica Ortiz de Montellano is based in Mexico and offers assistance in foods, packaging and preservation. She is an expert in food design and process developments including structure, formulation and additives including Thermal Process controls and records for Aseptic Processing and Packaging Systems including microbiological testing for Aseptic Production and CIP programs for Aseptic Systems. In addition, she conducts analyses of packaging materials and utensils to analyze stability, migration, contamination, flavor degradation and more.

EAS Blogs on Proposed Efficiencies in Pharma Manufacturing

EAS regulatory intern Neha Mookuparambil authored a blog for ISPE iSpeak on FDA’s Proposed Approach to Improve Efficiencies for the Advancement of Pharma Manufacturing through Continuous Manufacturing. The FDA has been pushing for advanced manufacturing processes in the pharmaceutical industry. The efficiency, consistency, reliability and ease with adoption of CM could provide for cost benefits and timely supply of drugs.

FDA Strengthens Process of Initiating Voluntary Recalls

Voluntary recalls are a vital means to protect public health and typically are the quickest way to remove defective or potentially harmful food, medical, and consumer products from the market. FDA’s new Draft Guidance includes steps companies may take to plan, prepare and initiate a voluntary recall in the event of a problem. The Guidance includes information on employee training, record keeping and written procedures for executing a recall. Companies in need of assistance in developing these tools or who feel a voluntary recall is warranted may contact EAS for assistance. 

Final Guidance for Abbreviated Drug Application Submissions

FDA has issued Final Guidance related to drug marketing application submissions for human drugs and recommendations for considerations of whether to submit a 501(b)(2) New Drug Application, commonly referred to as an NDA, or a 505(j) Abbreviated New Drug Application, commonly referred to as an ANDA. These are two of the four available pathways for drug submissions for FDA approval, with ANDA known as an abbreviated pathway.

While an NDA is required for all new drug products, administration routes, etc, an ANDA may be an appropriate submission for products which duplicate a previously reference listed drug (RLD) that FDA has already determined is safe and effective. In such cases where the active ingredient(s), dosage form, route of administration, strength, previously approved conditions of use, and labeling (with certain exceptions) mimic that of a RLD, an ANDA may be appropriate. ANDAs must still include full investigative reports of safety and effectiveness, and may also rely on FDA’s previous finding of such to the extent that the proposed drug shares the same characteristics as the RLD.

It is important to note that in cases where an ANDA is the appropriate submission choice, FDA will reject a 501(b)(2) application as a duplicate of an RLD. Therefore, a thorough consideration of the drug under submission compared to RLDs already approved by FDA is warranted. Firms wishing to outsource this review and seek recommendations on the appropriate FDA filing are invited to contact Bryan Coleman, Senior Director of Drugs and Medical Devices.

Couch to Present at World Tea Expo

Tara Lin Couch, Ph.D., Senior Director of Dietary Supplement and Tobacco Services will present a session on “Dietary Supplements or Food – What is Tea?” at the World Tea Expo which is being held June 10-13, 2019 in Las Vegas. With the enforcement of provisions under FSMA and FDA’s dedicated review of ingredients it considers to be DSHEA, understanding how to market teas, powders and botanicals has never been more critical. Join Tara on June 12, 2019 for her presentation.

EAS to Exhibit at IFT Annual Meeting

Join EAS Chairman and CEO, Ed Steele, President and COO, Dean Cirotta and Director of Labeling and Cosmetics, Cathryn Sacra at the EAS booth #424 on June 3-5, 2019 at the IFT Annual Meeting in New Orleans. Discuss regulatory needs pertaining to foods and dietary supplements and learn how EAS can assist your firm. Interested in registering for our fall food and dietary supplement compliance seminars? Stop by the EAS booth to pick up our special IFT registration discount code.

May 2019 Drug and Device Corner

Guidance Document updates on the FDA website