If you haven’t yet registered there are still a few weeks left before our compliance seminars taking place in Long Island this April. For more information, agendas, pricing and link to register, visit our seminars webpage. We invite you to join us for these two-day information-rich events.
Dr. Nico van Belzen is an advocate of food safety and nutrition. Formerly, Dr. van Belzen held managing director positions at the International Dairy Federation (IDF) and the European branch of the International Life Sciences Institute (ILSI) which he represented towards FAO, WHO, Codex, EFSA and other intergovernmental organizations. He has also held R&D management positions at DMV International where he was involved in product development, biochemical and physical analyses of food ingredients and pharmaceutical excipients, marketing support, business development and due diligence.
The FDA has published a revision to Manual of Policies and Procedures 5240.3, Prioritization of the Review of Original ANDAs, Amendments, and Supplements. This update is designed to efficiently allocate limited agency resources to areas where priority review is most likely to meaningfully increase generic drug access and ensure fairness to applicants. Details can be found on the FDA webpage. Additionally, the agency has a prerecorded webinar describing the revisions.
The FDA published a Guidance Document, Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, which describes how sponsors and applicants must organize the content that they submit to the Agency electronically for all submission types under section 745A(a) of the FD&C Act. Of note, this guidance also describes the addition of exemptions and waivers from complying with eCTD requirements. Exempted from the eCTD Requirements are all Type III DMF submissions. Although these specific submissions will be exempt from filing in eCTD format as described in this guidance, FDA still encourages applicants to send submissions in an alternative electronic format (e.g., PDF files following the CTD structure). See the Guidance Document for further exemptions and waivers.
Below noted CDER Product-Specific Guidances have been withdrawn as of 22 January 2020:
|Active Ingredient||Type of Guidance||Route & Dosage Form||RLD|
|Butenafine Hydrochloride||Draft||Topical dream||21408|
The Agency has launched The Compilation of Center for Drug Evaluation and Research (CDER) New Molecular Entity (NME) Drug and New Biologic Approvals, a new resource designed to assist external and agency researchers collecting historical information about FDA’s drug approvals. This .csv file with curated data regarding drug products approved by CDER since 1985, will be available on the agency’s website.
The FDA is requesting voluntary withdrawal of bacitracin for injection from the market. In April 2019, the Antimicrobial Drugs Advisory Committee met and discussed the safety and effectiveness of bacitracin for injection. The advisory committee voted almost unanimously, with one abstention, that the risks outweigh the benefits for the drug’s only approved indication. Based on FDA’s review of currently available data, FDA believes that the potential problems associated with bacitracin for injection are sufficiently serious to remove the drug from the market. This requested voluntary withdrawal does not impact approved topical or ophthalmic drugs that contain bacitracin.
The FDA is hosting a Public Meeting regarding Communications about the Safety of Medical Devices. During this public meeting the FDA hopes to hear from all stakeholders, including patients and caregivers, healthcare providers, regulated industry, and media. The FDA is looking for feedback on how the agency can improve their safety communications to assure stakeholders receive the information they need in a timely, clear, and consistent manner. A preliminary agenda has been published. Details can be found on the website for participation.
CVM Broadcast #39 notice was issued 7 February 2020. The OSC DER eSubmitter Program will soon require digital signatures on electronic submissions to be registered with the CVM Electronic Submission System (ESS). We expect this requirement to be implemented as early as mid-March 2020. If you have questions, please contact CVM at email@example.com.
CVM Broadcast #40 notice was issued 13 February 2020. CVM is updating their CVM Submission Type list of values in response to feedback from stakeholders when submitting Manage Forms to CVM. This change will occur on February 22, 2020 in FDA ESG Pre-Production and February 29, 2020 for FDA ESG Production. This update will modify the Submission Type list of values for CVM: 1] Submission Type “Electronic_Submissions” will be changed to “Manage_Form”. Stakeholders should use this folder when submitting Manage Form submissions to CVM. 2] Submission Type “eSubmitter” should be used for any eSubmitter submission to CVM 3] Submission Type “Adverse_Events_Reports” should be used for any electronic adverse event report submission to CVM.
Guidance Document updates on the FDA website
Hypertension Indication: Drug Labeling for Cardiovascular Outcome Claims – This guidance is intended to assist applicants in developing labeling for cardiovascular outcome claims for drugs that are indicated to treat hypertension.
CDER & CBER
Promotional Labeling and Advertising Reference and Biosimilar Products Questions and Answers – This guidance addresses questions firms may have when developing FDA-regulated promotional labeling and advertisements (promotional materials), for prescription reference products licensed under 351(a) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(a))
Mucopolysaccharidosis Type III (Sanfilippo Syndrome): Developing Drugs for Treatment – The purpose of this guidance is to provide recommendations to sponsors regarding eligibility criteria, trial design considerations, and efficacy endpoints to enhance clinical trial data quality and foster greater efficiency in development programs for drugs to treat mucopolysaccharidosis type III (MPS III; also called Sanfilippo syndrome).
Biosimilars and Interchangeable Biosimilars: Licensure for Fewer Than All Conditions of Use for Which the Reference Product Has Been Licensed – This guidance provides recommendations to applicants seeking licensure under section 351(k) of the Public Health Service (PHS) Act of a proposed biosimilar or proposed interchangeable biosimilar for fewer than all of the reference product’s licensed conditions of use.
Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachments – This document provides current specifications for submitting individual case safety reports (ICSRs) and ICSR attachments in electronic form.
Arthroscopy Pump Tubing Sets Intended for (510(k)) Submissions – This draft guidance document provides recommendations for 510(k) submissions for arthroscopy pump tubing sets intended for multiple patient use. These devices are designed to deliver irrigation fluid to the surgical site, such as knee, shoulder, hip, elbow, ankle, and wrist joint cavities, during arthroscopic procedures.
Peripheral Vascular Atherectomy Devices – Premarket Notification [510(k)] Submissions – This guidance document provides recommendations for 510(k) submissions for peripheral vascular atherectomy devices. The recommendations reflect current review practices and are intended to promote consistency and facilitate efficient review of peripheral vascular atherectomy submissions.
Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations – This guidance provides FDA’s current thinking on determining sameness of human gene therapy products under FDA’s orphan drug regulations for the purpose of orphan-drug designation and orphan-drug exclusivity.
Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up – FDA is providing sponsors of retroviral vector-based human gene therapy products, recommendations regarding the testing for RCR during the manufacture of retroviral vector based gene therapy products, and during follow-up monitoring of patients who have received retroviral vector-based gene therapy products.
Long Term Follow-up After Administration of Human Gene Therapy Products – FDA is providing sponsors who are developing a human gene therapy product (GT Product), recommendations regarding the design of long term follow-up studies (LTFU observations) for the collection of data on delayed adverse events following administration of a GT product.
Human Gene Therapy for Retinal Disorders – This guidance provides recommendations to sponsors developing human gene therapy (GT) products for retinal disorders affecting adult and pediatric patients.
Human Gene Therapy for Rare Diseases – This guidance provides recommendations to sponsors developing human gene therapy (GT) products intended to treat a rare disease in adult and/or pediatric patients regarding the manufacturing, preclinical, and clinical trial design issues for all phases of the clinical development program.
Human Gene Therapy for Hemophilia – This guidance provides recommendations to sponsors developing human gene therapy (GT) products for the treatment of hemophilia including clinical trial design and related development of coagulation factor VIII (hemophilia A) and IX (hemophilia B) activity assays, including how to address discrepancies in factor VIII and factor IX activity assays.
Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs) – FDA is providing sponsors of human gene therapy Investigational New Drug Applications (INDs), recommendations regarding chemistry, manufacturing, and control (CMC) information submitted in an IND.
Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components – FDA is issuing this guidance document to provide blood establishments that collect blood and blood components, with revised recommendations intended to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood components.
Use of Serological Tests to Reduce the Risk of Transfusion-Transmitted Human T-Lymphotropic Virus Types I and II (HTLV-I/II) – We, FDA, are providing you, blood collection establishments, with recommendations regarding the use of serological tests to reduce the risk of transmission of human T-lymphotropic virus type I (HTLV-I) and type II (HTLV-II), collectively referred to as HTLV-I/II, by blood and blood components. These recommendations apply to the collection of Whole blood and blood components, except Source Plasma.
CVM GFI #108 Registering with CVM’s Electronic Submission System – This guidance provides general standards which should be used to register with the Center for Veterinary Medicine (CVM or the Center) Electronic Submission System (ESS).
CVM GFI #191 Changes to Approved NADAs – New NADAs vs. Category II Supplemental NADAs – This guidance is intended to assist sponsors who wish to apply for approval of changes to approved new animal drugs that require FDA to reevaluate safety and/or effectiveness data.
Draft Guidance for comment purposes only
Nonclinical Safety Evaluation of the Immunotoxic Potential of Drugs and Biologics – The purpose of this guidance is to assist sponsors in their nonclinical evaluation of the immunotoxic potential of drugs and biologics by supplementing the recommendations on nonclinical immune system assessments provided across the following guidance documents: 1] International Council for Harmonisation (ICH) guidances for industry, 2] S8 Immunotoxicity Studies for Human Pharmaceuticals (April 2006), 3] M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (January 2010), 4] S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (May 2012) and 5] S5(R3) Detection of Toxicity to Reproduction for Human Pharmaceuticals (November 2017)
EAS independent consultant Kathy Knutson, Ph.D. discussed the importance of allergen controls and employee training in an article published in Food Safety Strategies. “Allergen management training… must be at the same intensity [as that of training]… on the management of pathogens,” she says. EAS offers a robust review of allergen and pathogen management as well as capabilities to develop customized in-house training programs that enable your employees to gain the skills they need in your own facilities.
David Cockram, Independent Consultant, EAS Consulting Group, LLC
We live in exciting times, with new discoveries being announced daily about the relationships between nutrition, diet, health, and disease. So much so that it’s often hard to keep track of whether this food or food component is currently something we should be eating more or less of at the moment (think eggs or caffeine). At the same time, these discoveries create opportunities for new nutritional products to help maintain health, optimize physical performance, avoid disease, slow progression of a chronic condition, or manage an existing condition. A food or food ingredient that prevents or treats a disease sounds like a great commercial opportunity, right? How about omega 3s, CLAs, plant proteins, probiotics, prebiotics, individual amino acids, tropical plants and their fruits and seeds, “pre-digested” fats and carbohydrates?
From a regulatory standpoint, however, food products making therapeutic claims are very challenging. While most countries allow foods to make claims about their value in maintaining normal nutritional status and function, opportunities to make claims about disease risk reduction generally are either prohibited or permitted only in the context of approved health claims (claims about the relationship between the potential reduction in the risk of developing a disease and nutrition). Going a step further and making claims about treating or preventing an existing disease or condition, even where the evidence is clear that the claim is truthful and not misleading, is permitted only under very limited circumstances for foods. For products where the intended use is for therapeutic purposes, medical foods are a very limited category of foods that can make claims for dietary management of a disease or condition (but not that they prevent, treat, or cure anything). Developing a product positioning, adequate substantiation, and claim language that is both compliant but also commercially compelling is challenging but not impossible.
What can be done to assure success from a regulatory standpoint? Some pieces of the puzzle are clear, such as assuring that the finished product is safe and effective for its intended use, all components are permissible food ingredients, and packaging materials are acceptable for use. Design a product using solid science to support the intended benefits. Where products are intended for a multinational launch, early consideration of all country’s regulatory requirements (permitted ingredients, claims, packaging, substantiation standards, data needed for approval of novel ingredients, and review timelines) is critical. Fortunately, the basic data package is pretty standard across countries; however, formatting, review timelines, and fine points of data submissions vary widely so regulatory considerations must be a high priority throughout the formulation and product development process.
Other parts of the compliance puzzle, particularly in the area of product claims tend to be grayer and potentially subject to different interpretations. What a marketer may view as an awesome claim about their new food product may to a regulator be a violative drug claim that garners enforcement action for the company. Product claims must be substantiated using soundly designed and statistically-powered studies that clearly support the express and implied product benefits and label claims. Such studies in humans can be challenging to conduct and interpret for a number of reasons (e.g., all humans need to eat so careful attention to trial design is needed to detect the incremental effect of a product or nutrient beyond the baseline diet, free will and other causes of non-adherence to study protocols, etc.). To overcome the challenges of studying humans, preclinical designs are frequently used as partial substantiation for claims. However, increasingly regulatory bodies are unwilling to accept preclinical data as a sole source for substantiation for benefit claims in humans. Sometimes a premarket consultation with regulatory agency staff such as that provided by EAS can provide helpful guidance…but it can also yield challenging feedback that can only be ignored at great risk.
An infrequently discussed issue is the risk tolerance of the company around product positioning and claims. Where on the spectrum of risk does your company fall? It can range from ‘get a warning letter from a regulatory agency and you are fired’ to ‘if we don’t get an occasional warning letter then you’re obviously not pushing the envelope enough’. Keep in mind that agency enforcement action is enormously time-consuming and disruptive to the company and can quickly derail any product development, marketing and launch effort. This knowledge, along with an understanding of Agency expectations and historical enforcement activities will go a long way to helping a product development and marketing professional appropriately calibrate product claims and claim substantiation.
In the end, careful planning and early discussion between product development, clinical science, labeling and marketing staff are needed to assure that the product meets all needs including regulatory, as cost- and time-efficiently as possible. An experienced regulatory professional must have a seat at the table throughout the process to help the organization balance commercial objectives and desires with Agency expectations and EAS Consulting Group with over 150 Independent Consultants under contract has expertise in all of these areas.
Jim Goldman, CPP, is a certified packaging expert with a consistent history of achievement in developing packaging, supply chain, and production equipment for the Consumer Products industry. He is an innovative business partner with the ability to create a vision for change and the roadmap to introduce new products and processes efficiently. His broad packaging technical knowledge includes deep experience in glass containers including fracture analysis. Jim is frequently asked to service as an expert witness in legal matters.
EAS director, Cathryn Sacra, and independent consultant, Tom Jonaitis, will represent EAS at the Society of Toxicology Annual Meeting taking place in Anaheim, March 15-19, 2020. On hand to discuss EAS toxicology capabilities pertaining to GRAS and NDI submissions, EAS offers this comprehensive technical service to all companies seeking FDA support for novel ingredients. Please stop by the EAS booth #761 while at SOT or make an appointment to speak with Cathryn and Tom directly.
Cesar Matto assists clients with pharma GMP compliance. He is experienced in all forms of solid dosages, ensuring positive outcomes, through the creation and implementation of successful transitions in development projects through clinical manufacturing, regulatory approval, conformance and commercial manufacturing. Additionally, he has a history of successful implementation of GMP remediation activities.
Preventive Controls for Animal Food/Feed is a requirement for all manufacturers of animal food/feeds. EAS expert, Jerry Poley, who assists clients with food safety audits including requirements for HACCP, FAMI QS, FPA Safe, PAACO (Professional Animal Auditor Certification Organization) as well as evaluation of nutrition, composition, safety, quality, regulatory issues and training programs explains:
Poley: The Preventive Controls for Animal Food (PCAF) regulation is found in Title 21 of the Code of Federal Regulations part 507 (21 CFR part 507). The PCAF regulation applies to all facilities that manufacture, process, pack or hold animal food for consumption in the United States (21 CFR 507.5(a)). Enforcement dates have passed so all animal food companies need to be in compliance with the PCAF Rule, although so far, FDA has not taken a strong enforcement stance against any company producing an animal food unless there was evidence the food caused an illness in the animal consuming it or to the human animal owner, i.e. imported processed pig ears for dogs. All animal food manufacturing facilities, foreign or domestic must be registered with FDA and for foreign manufacturing facilities, have a “US Agent” (a service which EAS provides). This is different than the US Agent used for US Customs and Border Protection.
Animal food is defined in Title 21 of the Code of Federal Regulations (21 CFR 507.3) as food for animals other than man and includes pet food, animal feed, raw materials and ingredients. Hummingbird food, for example, is one area of confusion for the animal food industry because it is primarily sugar in water. However, hummingbird food is considered animal food and is regulated as such. Therefore, if it is intended for consumption by animals in the US, it would be subject to the PCAF regulation.
In addition to the PCAF regulation, the US importer of any animal food would be subject to the requirements of the Foreign Supplier Verification Program (FSVP) regulation, which requires that there be an FSVP “Importer’s Office”, geographically located in the US and a written animal food safety and risk assessment program is developed and available at the FSVP Importer’s Office for review and inspection by FDA.
Depending on certain factors regarding the Canadian manufacturing facility, such as size and if the facility is a personal residence, different registration and regulations will apply.
For more PCAF information see FDA’s fact sheet. For more information on EAS capabilities in foods click here. Companies importing animal or human foods into the US may wish to view our complimentary on-demand regulatory webinars, including topics such as requirements for a Qualified Individual, the role of a US Agent, FSVP requirements (offered both in English and Spanish) and more. View our on-demand webinars page here.
The challenge of detecting Food Fraud has never been greater nor the economic loss to food manufacturers, importers, retailers and consumers. If you haven’t already registered it is not too late to join EAS Independent Consultant Dr. Mehrdad Tajkarimi on March 4, 2020 at 1pm eastern for a deep dive into the latest and greatest technologies in food fraud detection and their applications.
April Kates shared insights into the multi-pronged approach of FDA’s Nutrition Innovation Strategy which includes modernizing food labeling, including food standards, health claims policy, ingredient labeling requirements as well as continuing forward with the implementation of the updated nutrition facts label, menu labeling, and reducing sodium in processed food products.
The benefits of EAS being a part of the Certified Group of companies are really starting to gain momentum and our clients are beginning to take advantage of the synergies between EAS, Certified Laboratories, Labstat and Labs-Mart. EAS is now assisting Certified clients with regulatory consulting services, labeling and more, while EAS clients are enjoying the benefits of having access to best in class laboratory testing solutions.
With expanded offerings also comes an opportunity to improve our services and look – you’ll soon find the EAS website updated and enhanced to reflect our membership in the Certified Group of companies and to provide easier navigation and quicker access to the critical information EAS is known for providing: Reliable Regulatory Content.
Our new website will allow you to more easily find the information you need, such as articles written by EAS independent consultants and staff, complimentary on-demand webinars that offer deeper dives into important current compliance issues and of course, detailed information about EAS services and capabilities in regulatory consulting, training and auditing.
We are very excited for you to see our new website and look forward to continuing to be your trusted partner for FDA regulatory solutions. As we develop the new website, we will continue to provide pertinent updates and information through our email and LinkedIn channels. We anticipate an early April launch of our new website so If you aren’t already linked with EAS please take the opportunity do so and stay tuned for our new and exciting website!
Tim Kapsala works with EAS pharmaceutical clients to identify compliance gaps and deficiencies through audits and mock-FDA inspections, preparing reports documenting significant observations and providing recommendations to be used in remediation activities. Additionally, he performs mock FDA pre-approval audits prior to NDA and ANDA submissions, with audit capabilities including APIs, OTCs, pre-filled syringe biosimilars, due diligence, internal audit evaluation, pre-inspection readiness, distributor/vendor qualification, contract laboratory, contract manufacturer, and more.
EAS is honored to be an instructor for two FDLI events this month. First, Gisela Leon will present on general requirements of labeling at the Intro to Food Law and Regulation on March 24-25, and Allen Sayler will provide a recall recap, looking at FDA enforcement actions in the past year on March 26 at the Food Enforcement and Compliance conference. Both events will be held in Washington, D.C.
Is your manufacturing floor a safe work environment? Do you abide by OSHA controls commonly known as Lockout-Tagout? Employees can be seriously or fatally injured when machinery they clean, service or maintain unexpectedly energizes, starts up, or releases stored energy. Join EAS independent consultant, Jon Anderson for this complimentary webinar on OSHA’s Lockout-Tagout on April 16, 2020 at 1pm eastern.
Charlotte Peyton discussed recent regulatory and business changes in the hemp industry in Natural Products Insider. Regulators are working to get a handle on the unbridled hemp and CBD markets, while finished product brands are seeking out strategies for testing and the supply chain. If this is your business, EAS can help.
David Cockram assists EAS clients in the areas of GRAS, Infant Formula and NDI study design through the execution and support of safety submissions for novel foods, dietary ingredients and nutritional products. He recently retired as Senior Director of Global Regulatory Science and Innovation at Abbott Nutrition. David holds a PhD from The Ohio State University in Nutrition. He is an author or inventor of 25 scientific papers, book chapters, webinars, and patents.