OTC Drug Monographs, Past, Present, and Future – Part 1

OTC Monograph Regulations a Five Part Webinar Series

Join EAS Independent Advisor for OTC Drugs and Labeling, Susan Crane, as she explores the history of OTC Monographs, why reforms are necessary and being undertaken now, and how OTC drug companies can expect those changes to impact their labels in the future in a five-part series.

Ensuring Regulatory Compliance of GMP Laboratories

April 23, 2019

Denver, CO

This one-day intensive program will discuss FDA’s current Good Manufacturing Practice (GMP) requirements for Research and Development and Quality Control Laboratories. The course will cover GMP regulations for physical, analytical, and microbiological laboratories including analyst training and qualification; the labs’ physical facility and environment; instrument qualification, calibration and maintenance programs; laboratory sample control processes; the management of standards and chemicals; the management of data; and overall laboratory documentation. The development, verification, validation, control, and use of test methods as well as transfer thereof will also be discussed. An entire session will be dedicated to the performance of thorough, timely, unbiased, well-documented, and scientifically sound Out-of-Specification (OOS) investigations since this is one of the most critical laboratories quality systems. Tips regarding establishing quality agreements with clients and handling the FDA during an inspection will also be provided.

FDA issues of concern will be highlighted throughout the program with emphasis placed on recent FDA regulatory or administrative actions. All of this will allow participants to gain an understanding of the importance of laboratory GMPs and how to meet FDA’s requirements.

Registration

$600

Register

Discounts

Group Rate, two or more from the same firm – 10% per person (GROUP10)
Federal/State Government Employees – 10% per person (GOV10)

Registrants with Promotion codes - Limit one Promotion code per transaction

Includes:

  • Training manual with the slide presentation
  • lunch

Dates and Location

April 23, 2019

Hilton Garden Inn Denver Downtown
1400 Welton St.
Denver, CO 80202

Instructor

Tara Lin Couch, Ph.D., Senior Director, Dietary Supplement and Tobacco Services

Tara Lin Couch Ph.D.Dr. Couch is a Ph.D. Analytical / Organic Chemist with over 25 years of diverse laboratory and regulatory experience in academic, field, contract, and manufacturing environments. She possesses exceptional analytical abilities as demonstrated also by her B.S. in Mathematics. She has served as the Study Director on numerous EPA and clinical studies as well as directed the Quality Control department at a pharmaceutical and dietary supplement manufacturing facility. The latter entailed directing all aspects of the quality control analytical and microbiological laboratories including management of the company Stability Program and Quarantine Area operations. Dr. Couch also provided scientific expertise and technical support for new product development, product reformulations, and on-going production challenges. She served as the scientific head of a Strength and Purity Verification Testing Program committee, which provided full label claim testing on dietary supplements to meet all Dietary Supplement Health and Education Act (DSHEA) regulations and expectations of the FDA. Her talents were also utilized to evaluate and set raw material and finished product specifications and prepare product summaries (white papers) for dietary supplement products.
As a consultant, Dr. Couch has assisted numerous dietary supplement companies with the development, improvement, and implementation of strong Quality Systems that are scientifically sound, efficient, practical and compliant with all FDA regulations. She is an experienced speaker having presented numerous scientific and regulatory compliance lectures around the country, conducted in-house and external Dietary Supplement GMP trainings, and taught entry level to graduate level chemistry courses and laboratories at several academic institutions.

Who Should Attend?

This program would benefit individuals involved in the Regulatory Affairs, Quality Control/Quality Assurance, Manufacturing, Research & Development, Validation/Qualification, laboratory analysts, supervisors, and managers. It will be of particular interest to those charged with implementing, validating and maintaining laboratory compliance programs.

Minimum Registration Policy

  • Should the minimum enrollment number for the seminar not be met, EAS has the right to cancel within 45 days of the training and refund the registration fee in full.

Cancellation Policy

  • Cancellations received before 46 days prior to the training event will result in a $95 processing fee. No refunds will be given for cancellations received after that date. Substitutions will be allowed as long as notice is given to EAS in advance.

For More Information

Government Shut Down Impacts FDA and Industry Operations

As the Government Shut Down continues, FDA recently announced that agency operations will continue to the extent permitted by law, maintaining core functions that address imminent threats to the safety of human life as well as activities funded by carryover user fee funds. FDA will continue to respond to emergencies – such as monitoring for and quickly responding to outbreaks related to foodborne illness and the flu; support high-risk food and medical product recalls when products endanger consumers and patients and pursue civil and criminal investigations as appropriate and continue screening food and medical products that are imported to the U.S.. Mission critical surveillance for significant safety concerns with medical devices and other medical products will also continue. During this period of lapsed funding, however, FDA does not have legal authority to accept user fees assessed for FY 2019 until an FY 2019 appropriation or Continuing Resolution for the FDA is enacted. This includes regulatory submissions for FY 2019 that require a fee payment and that are submitted during the lapse period.

Steps to Develop Compliant SOPs Discussed in AHPA Report

The December American Herbal Products Association (AHPA) Report (subscription required) included an EAS authored article on steps to develop fully compliant Standard Operating Procedures. Though the development and detail of each SOP is at the discretion of individual companies, they should provide a thorough manual that enables each employee to understand their roles and responsibilities and how to perform and document them with regard to the cGMPs. As current practices evolve, so too should SOPs as they are designed to be living documents, representing best practices and required procedures.

FDA Encourages Innovation and Safety as Part of Medical Device Regulatory Overhaul

EAS authored an article in MedTech Intelligence on FDA’s efforts at encouraging innovation while keeping a close eye on safety as part of a medical device regulatory overhaul. FDA is working to retire outdated predicates for 510(k) submissions as well as improve their post-market surveillance system through a multi-collaborative effort called National Evaluation System for Health Technology (NEST).

Couch Shares Thoughts on Contract Laboratory Best Practices as Part of Insider Q&A

Senior Director for Dietary Supplement and Tobacco Services, Tara Lin Couch, Ph.D. participated in a discussion with other industry leaders on best practices for contract laboratories in a recent Natural Products Insider. Contract labs are often enlisted to certify that products are fully and validly tested, and the relationship with these labs can sometimes be complicated by a lack of provided material and product matrix information to ensure that appropriate, scientifically valid test methodologies are used. Couch and her industry colleagues share thoughts on how to convey expectations and develop agreements.

Join EAS for Complimentary Webinar Series on OTC Monograph Reforms

Join EAS Independent Advisor for OTC Drugs and Labeling, Susan Crane, as she explores the history of OTC Monographs and how OTC drug companies can expect updates to the Monograph system to impact their labels in a webinar series starting January 16, 2019. Part one will discuss the history of OTC monographs and why reforms are necessary. Part two is February 27, 2019 and will discuss understanding the FDA and FTC Labeling and Claim Requirements for Cosmetic and Homeopathic products in the OTC market. The final sessions, with dates to be announced will discuss what makes a drug an OTC and the Monographs Compliance System; and GMP obligations – understanding how the GMPs are Applied and how to prepare for FDA Inspection. Reserve your seat today!

Drug and Device January 2019

Guidance Document updates on the FDA website

All centers:

Developing and Labeling In vitro Companion Diagnostic Devices for a Specific Group or Class of Oncology Therapeutic Products

CDER:

Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis:  Developing Drugs for Treatment

Post-Complete Response Letter Meetings Between FDA and ANDA Applicants

Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act

CDER & CBER:

New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2)

Questions and Answers on Biosimilar Development and the BPCI Act

The “Deemed to be a License” Provision of the BPCI Act Questions and Answers Guidance for Industry

Interpretation of the “Deemed to be a License” Provision of the Biologics Price Competition and Innovation Act of 2009

Biomarker Qualification: Evidentiary Framework

Data Integrity and Compliance With Drug CGMP Questions and Answers

Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics

Developing and Submitting Proposed Draft Guidance Relating to Patient Experience Data

CDRH & CBER:

User Fees and Refunds for Premarket Approval Applications and Device Biologics License Applications

CDRH:

Recommendations for Dual 510(k) and CLIA Waiver by Application Studies

Select Updates for Recommendations Select Updates for Recommendations Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic Devices

Self-Monitoring Blood Glucose Test Systems for Over-the-Counter Use

Blood Glucose Monitoring Test Systems for Prescription Point-of-Care Use

Clarification of Radiation Control Regulations For Manufacturers of Diagnostic X-Ray Equipment

Breakthrough Devices Program

CBER:

Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion

Labeling of Red Blood Cell Units with Historical Antigen Typing Results

CVM:

Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food-Producing Species: Study Design Recommendations for Residue Studies in Honey for Establishing MRLs and Withdrawal Periods

2019 Produce Compliance Dates for FSMA

By Charles Breen, EAS Independent Advisor for FSMA Consulting Services

January 28, 2019, marks the compliance date for four categories of produce growers:

  • Sprouts from Very Small Farms (with certain exemptions), 
  • Sprouts from Very Small Farms eligible for a qualified exemption to comply with other requirements in 112.6 and 112.7, 
  • Other small farms, (except those with certain water requirements), and 
  • Small Farms eligible for a qualified exemption to comply with other requirements in 112.6 and 112.7

must come into compliance.

FSMA’s Final Rule on Produce Safety, Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption, and FDA’s helpful Small Entity Compliance Guide concerning determination of business size (based on annual monetary value of the food farms sell directly to qualified end users) are two important resources for farms growing and harvesting produce for consumption without further processing.

Recent foodborne illness outbreaks from romaine lettuce illustrate why it is prudent to take a fresh look at some specific areas where the introduction and harboring of pathogens can wreak havoc and cause devastating public health and economic consequences.

FDA’s recently announced that the list of possible growing areas identified as the source of the E. coli outbreak in romaine lettuce has been narrowed to three California counties, and one farm in particular. However, FDA concedes that this does not explain all of the illnesses. As of December 13, 2018, traceback information from five restaurants in four states have identified 11 different distributors, nine different growers, and eight different farms as potential sources of the contaminated lettuce, so it is likely that the outbreak cannot be explained by a single farm, grower, harvester, or distributor. FDA continues to investigate.

It’s also not only E. coli causing produce industry woes. Listeria monocytogenes prompted recent recalls of pre-packaged salad products and asparagus, as did a summer outbreak of Cyclospora in melons and lettuce. 

Why are these events continuing to happen? FSMA’s many requirements were designed to prevent just such occurrences. Are growers not complying with the regulations because they are too difficult to understand, or too difficult to follow? Or are these outbreaks examples of Murphy’s law, that no matter the risk mitigation strategy, if something can go wrong, it will?

The answer, in my view, is yes to all three – and I’ll add that sometimes downstream consequences are not fully understood until it is too late. 

Take for instance, this past summer’s E. coli outbreak in romaine lettuce. The fact that after so many months FDA still cannot pinpoint the exact source of the outbreak suggests these companies and areas under investigation appear (at least on the surface) to be largely in compliance. As of this writing, Whole Genome Sequencing testing has identified only one result where an agricultural water reservoir sediment contains the same E. coli O157:H7 strand implicated in the outbreak. However, the agency says it isn’t clear how the water became contaminated and that additional illnesses demonstrate that this reservoir cannot be the only cause of such a widespread outbreak. 

As compliance dates for various sized produce and sprout farms arrive, FDA will continue to transition from an educational to a regulatory approach for FSMA and supplier enforcement. Prudent companies will take a step back and review their supplier, manufacturing, agricultural and transportation protocols to ensure that all conceivable entry points for microbiological, chemical and physical hazards are controlled, and, when problems do occur, quickly testing entry points to identify and reduce impacts.

Just because something hasn’t yet happened at your facility doesn’t mean it won’t, and don’t assume that just because something happens at one of your suppliers or distributors, that your company won’t see negative repercussions. Food safety is everyone’s business.

EAS stands ready to help you with all aspects of FSMA compliance. Contact us or more information end-users and we invite you to view our many industry information sheets to learn more about our services with regards to foods, FSMA and other FDA requirements for all product areas.

Dietary Supplement Specifications Development – Still Challenging the Industry Ten Years Later

By Tamika Cathey

Specifications Development, as defined in FDA’s Good Manufacturing Practices for dietary supplements (21 CFR §111) have posed one of the biggest challenges to industry since the inception of the requirements in June 2007. Specifically, 21 CFR §111.70 requires manufacturers to develop specifications for each component used in the manufacturing process and the finish product, including raw material components, in-process controls, packaging/labeling materials, and finished products. To be compliant with 21 CFR §111, each specification must ensure the quality of the material or product by addressing its identity, purity, strength or concentration, physical composition and lack of potential contaminants or ensuring that potential contaminants are present at acceptably safe levels. However, manufacturers continue to struggle with understanding specifications development and compliance. This is evidenced by the many Warning Letters and Form 483s issued by the FDA in the past ten years.

Certainly, the intent of specification requirements is well understood, at least conceptually by industry. The main purpose for requiring adequate specifications is to prevent product(s) adulteration and ensure that the finish product meets at least 100% of all nutrient claims declared on the Supplement Fact Panel (SFP) throughout its best by date or expiration date per 21 CFR §101.9 under the Nutritional Labeling and Education Act (NLEA). Once a specification is set, the specification must be verified using scientifically sound and justified testing analysis and/or visual examination analysis such as organoleptic, macroscopic, microscopic, chemical, or microbial. Recognized test methods can be obtained from compendial sources like USP monographs, AOAC, FCC, or NF and used a starting point in determining an appropriate method. Multiple tests and examinations are usually deployed to ensure specifications are met per 21 CFR §111.75 and 21 CFR §111.320. All of this ensures consistent reproducibility and reliability of a finished product that is either being manufactured or packaged.

A look at recent warning letters illustrates this lack of understanding with findings such as: 

  • A lack of or incomplete identity component specifications (e.g. dietary ingredients, excipients or process aids, coating materials etc.) for each component per 21 CFR §111.70(b)(1) and 21 CFR §111.70(b)(2).
  • Lack of or incomplete specification(s) for in-process controls in manufacturing process per 21 CFR §111.70(a).
  • Lack of or incomplete product specifications for finish products per 21 CFR §111.70(e) to include package/labeled products (e.g. 21 CFR §111.70 (d) & (f) & (g)).

Briefly, specifications are a set of defined parameters benchmarked against associated acceptance criteria providing characteristics and quality of a finish dietary supplement. The expectation is that when specifications are established, they will be written, managed in a controlled system with revision histories that are tracked, monitored, reviewed and approved by the Quality Department. This means materials and products being used from other sources will be unequivocally identified, the microbiological purity and other purity requirements will be assessed to determine strength and concentration of a dietary ingredient. The physical composition will be evaluated, and any potential contaminants will be identified.

When developing specifications, it is a good idea to begin as early as possible by identifying critical quality attributes of finish product(s) and the manufacturing process as a whole. These quality attributes are to be identified with acceptable ranges determined in order to assess the attribute. Scientifically sound/valid test methods and examinations are tools used to conduct the assessment. Each specification developed should address sections of identity, purity, strength, composition, and contaminants to meet regulatory requirements outlined in 21 CFR §111.

Dietary supplement manufacturers must consider component specifications, including dietary ingredients, as defined in 201(ff) of the FD&C Act and label claimed on SFP, and non-dietary ingredients such as excipients, capsules, and coating materials.

In addition, in-process specifications must be established for any point, step, or stage of manufacturing and packaging processes. Simply put, these specifications focus on verifying material composition thorough a series of physical tests and examinations such as in-process checks and metal detection. These specification requirements can be met by developing a comprehensive Master Manufacturing Record (MMR) as required in 21 CFR 111.210.

Packaging and labeling specifications for components including container closure systems and materials that may come in contact with finish product including desiccants, cotton, pouches, lids, outer cartons, labels, and inserts should include approved/qualified supplier information, name and description of item, and physical attributes such as material type, size, dimensions, and color. Physical attributes and item descriptions can be obtained from a reliable C of A. Keep in mind that packing specifications must be developed for every packing configuration used for finish products. Set process and control specifications within the MMR and set a requirement that visual examination for each batch will be performed.

Finally, finished product specifications (FP) establish the identity, purity, strength, composition, and limits of contaminates for each finished batch of dietary supplement. In short, the finish product specification details testing requirements for a finished batch. All dietary ingredients listed on the SFP must be identified on the FP specification and additional requirements of minimum and maximum acceptance criteria.

It is expected that the claimed SFP ingredients meet at least 100 percent of the label claim in order to meet the requirements NLEA detailed in 21 CFR 101.9. Release specifications may be set at a higher percentage to account for any needed overage amounts formulated into the product to ensure the 100-percent requirement is met throughout the product expiration date or best buy date.

In closing, specifications development can be established based upon acceptable ranges and values set forth by industry, academia, and scientific data/results from published journals, and/or product history in manufacturing. Refer to NLEA mandatory and voluntary labeling disclosure set forth by FDA 21 CFR 109 (j). Accredited laboratories and American Herbal Product Association can provide guidance for building the appropriate specification to include test method. Reference any sources used to determine appropriate specification. If further assistance is needed, manufacturers can also work closely with the qualified supplier(s), an accredited 3rd party laboratory, and/or qualified consultants to help with specification development.