Johnson & Johnson Consent Decree: A lesson in Drug cGMPs

The folks at Pharmalot have written an article about the Johnson & Johnson consent decree (http://tinyurl.com/4bxxl44).  The article includes a link to the consent itself, which details the cGMP requirements FDA expects to see at the drug manufacturer's facility. 

The consent decree details the systems that need to be set up to ensure that the company's drug products are produced properly and are safe and efficacious. The document makes clear that the plant needs to build a quality system from the ground up and is evidence of the catastrophic QA failure that lead to the recalls and the consent decree itself.  

My purpose in posting this information is not to spread salacious gossip but to provide what I think is useful information.  In my view, the consent decree can be used as a checklist to review the cGMPs at your manufacturing facility.  If you are unable to download the consent decree, please leave a comment with your email address and I will send it to you. (Your email address will not be published.)

Bioscience Translation & Application
Translating bioscience innovation into profitable applications.
www.BioTransApp.com

Liquid and Semi-solid Foods and Dietary Supplements

On March 3, 2011 FDA published a final rule that amended 21CFR 113, which regulates ‘thermally processed low acid canned foods in hermetically sealed containers” to allow the use of ‘temperature indicator devices’ other than mercury filled glass thermometers.  So why am I telling you about this?  Partly because what the agency calls ‘canned foods’, which brings to mind metal containers and possibly glass jars, also refers to other aseptically processed foods and beverages. But I tell you about this mostly because this modernization from mercury filled glass thermometers is not the agency’s only recent alertness to this general sector of regulations. You see, the sister regulations for ‘thermally processed low acid canned foods’ are regulations covering the production of ‘acidified foods’-- foods which are not aseptically processed because their pH is low enough to prevent spoilage.

So what?  Well, you and I and FDA have noticed many more liquid dietary supplements in the marketplace.  Most contain acid ingredients and therefore are acidified foods. However, not all manufacturers comply with the regulations of 21CFR114, which require that they register their facilities as acid food producers and file the processes by which they assure that the product will not spoil and cause public harm. This registration is separate from the more generic food facility registration. I wrote about this once before in November of 2010 but I am raising the issue again because I continue to see liquid dietary supplements that have acidic components added to them but whose processes have not be filed with FDA.  Because this regulation is important for ensuring the safety of public health, any violation could cause your company to have to cease production until FDA approves your process and your entire Good Manufacturing Practices (GMP) program. 

I am also concerned about these sister regulations because I have seen a number of liquid ‘alkalinizing’ products on the market—they too would fall under one of these sets of regulations.  The guidance documents for these regulations are really hard to find on the FDA website and an FDA staffer in the office of Low Acid Canned Foods agreed that the regulations are difficult to understand; none the less, if you are producing a liquid or semi-solid product that is preserved in any way, you probably need to pay attention to this. 

If you have any doubt about which regulations apply to your products, contact us by leaving a comment. We are here help.

If you know what regulations apply to your product but need help complying with them—let us know.

Effective today European Union ban bisphenol-A in plastic baby bottles

While the EU has banned the presence of  bisphenol-A in baby bottles (effective today), the FDA has not taken such a step. There was a joint Food and Agriculture Organization of the United Nations (FAO) and World Health Organization (WHO) expert meeting in November 2010 to review the toxicology and heath affects of Bisphenol-A (BPA).  This group proposed a safety assessment,


"In the light of these uncertainties about the possibility of adverse human health effects at low doses of BPA, especially on reproduction, the nervous system and on behavioural development, and considering the relatively higher exposure of very young children compared with adults, FAO and WHO will jointly organize an ad hoc expert meeting to assess the safety of BPA. Possible alternatives for BPA will also be considered and available information regarding uses and possible health concern will be summarized"

 However, the EU published a directive in January (http://tinyurl.com/4cjku7o) banning the substance.

BPA is used in the manufacture of polycarbonate plastic, the resin lining of cans, and other products; can be released from the plastics and resins by exposure to heat or acidic contents. According to scientists Frederick S. vom Saal and Claude Hughes, in a 2005 article in Environmental Health Perspectives, (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280330/) BPA has the following effects,
"Rate of growth and sexual maturation, hormone levels in blood, reproductive organ function, fertility, immune function, enzyme activity, brain structure, brain chemistry, and behavior are all affected by exposure to low doses of BPA."

The authors also note that 95% of Americans tested had measurable amounts of BPA in their urine.  Until FDA acts, it is up to each of us, particularly women of child-bearing age, to consider ways of limiting exposure to BPA such as curtailing or limiting use of products in cans and plastic bottles.

FDA's Agenda for 2011

Hello!!

I hope that the first 2 months of 2011 are going well for you and your business.  The information below was published in the Federal Register on December 20, 2010 but being that it is FDA’s published regulatory agenda, it is pertinent to any company regulated by FDA and provides a look at changes to anticipate. 

The Regulatory Flexibility Act of 1980 and Executive Order (EO) 12866 require that government agencies publish an inventory of rulemaking actions under development semi-annually so that we, the public, may be aware of and comment on the actions proposed on our behalf. (Not sure whether to grin or grimace here but that’s the story.)

There is something for everyone here.  FDA has been working since the 1960’s to update the monographs that regulate over the counter drugs—many of those remain on the agenda for 2011. In 2010 the agency proposed drastic changes to the process for medical device approvals and more ideas are noted on the agenda below.  Other highlights include upcoming rules on food labeling, infant formula GMPs, pet food labeling, and the use of cattle-derived ingredients in cosmetics as well as proposed rules affecting prescription drugs and biologics. New areas of FDA regulation—restaurant menus and tobacco products also made the agency’s ‘to do’ list.  The dietary supplement sector only makes the list for long term actions.

I have rearranged the agenda into product areas for your convenience.  To view the list as originally published visit http://www.gpo.gov/fdsys/ and search the Federal Register, Vol. 75, No. 243, December 20, 2010, p.79765-75767. The numbers preceding each listing are the sequence number and can be used to find more information about each rule when you visit the Federal Register. 

I would be happy to address questions you submit about these topics in future updates.  You may read past updates here on our blog, Bioscience FDA Update (http://biotransapp.blogspot.com/) . You are also invited to leave comments.

 

Food Pre-Rule Stage

311 Food Labeling: Safe Handling Statements, Labeling of Shell Eggs; Refrigeration of Shell Eggs Held for Retail Distribution

Food Proposed Rule Stage

328 Food Labeling: Nutrition Labeling for Food Sold in Vending Machines 

329 Food Labeling: Nutrition Labeling of Standard Menu Items in Chain Restaurants

Food Final Rule Stage

338 Use of Materials Derived From Cattle in Human Food and Cosmetics

339 Label Requirement for Food That Has Been Refused Admission Into the United States

Food Long Term Actions

355 Produce Safety Regulation .

356 Modernization of the Current Food Good Manufacturing Practices Regulation

Infant Formula Final Rule Stage

333 Infant Formula: Current Good Manufacturing Practices; Quality Control Procedures; Notification Requirements;

Records and Reports; and Quality Factors 

Dietary Supplement Long Term Actions

340 Current Good Manufacturing Practice in Manufacturing, Packing, Labeling, or Holding Operations for Dietary Supplements

Pet Food and Animal Feed Proposed Rule Stage

318 Import Tolerances for Residues of Unapproved New Animal Drugs in Food

320 Pet Food Labeling Requirements

321 Process Controls for Animal Feed Ingredients and Mixed Animal Feed

Cosmetic Final Rule Stage

338 Use of Materials Derived From Cattle in Human Food and Cosmetics

Over the Counter Drug Proposed Rule Stage

313 Over-the-Counter (OTC) Drug Review—Cough/Cold (Antihistamine) Products

314 Over-the-Counter (OTC) Drug Review—Internal Analgesic Products

315 Over-the-Counter (OTC) Drug Review—Laxative Drug Products

316 Over-the-Counter (OTC) Drug Review—Sunscreen Products

317 Over-the-Counter (OTC) Drug Review—Topical Antimicrobial Drug Products

322 Over-the-Counter (OTC) Drug Review—Pediatric Dosing for Cough/Cold Products

Over the Counter Drug Final Rule Stage

334 Over-the-Counter (OTC) Drug Review—Cough/Cold (Bronchodilator) Products

335 Over-the-Counter (OTC) Drug Review—Cough/Cold (Combination) Products

336 Over-the-Counter (OTC) Drug Review—External Analgesic Products

337 Over-the-Counter (OTC) Drug Review—Skin Protectant Products

Over the Counter Drug Long Term Action

341 Over-the-Counter (OTC) Drug Review—Cough/Cold (Nasal Decongestant) Products

342 Over-the-Counter (OTC) Drug Review—Labeling of Drug Products for OTC Human Use

343 Over-the-Counter (OTC) Drug Review—Ophthalmic Products

344 Over-the-Counter (OTC) Drug Review—Oral Health Care Products

345 Over-the-Counter (OTC) Drug Review—Vaginal Contraceptive Products

346 Over-the-Counter (OTC) Drug Review—Weight Control Product

347 Over-the-Counter (OTC) Drug Review—Overindulgence in Food and Drink Products

348 Over-the-Counter (OTC) Drug Review—Antacid Products

349 Over-the-Counter (OTC) Drug Review—Skin Bleaching Products

350 Over-the-Counter (OTC) Drug Review—Stimulant Drug Products

351 Over-the-Counter (OTC) Drug Review—Antidiarrheal Drug Products

352 Over-the-Counter (OTC) Drug Review—Urinary Analgesic Drug Products

353 Over-the-Counter (OTC) Drug Review—Certain Category II Active Ingredients

Medical Device Proposed Rule Stage

319 Laser Products; Amendment to Performance Standard

324 Unique Device Identification

327 General Hospital and Personal Use Devices: Designation of Special Controls for Infusion Pumps

Medical Device Final Rule Stage

331 Medical Gas Containers and Closures; Current Good Manufacturing Practice Requirements

Tobacco Product Proposed Rule Stage

325 Cigars Subject to the Family Smoking Prevention and Tobacco Control Act

326 Cigarette Warning Label Statements

Prescription Drug & Biologics Proposed Rule Stage

312 Electronic Submission of Data From Studies Evaluating Human Drugs and Biologics 

323 Electronic Distribution of Content of Labeling for Human Prescription Drug and Biological Products

Prescription Drug & Biologics Final Rule Stage

330 Postmarketing Safety Reporting Requirements for Human Drug and Biological Products

332 Content and Format of Labeling for Human Prescription Drugs and Biologics; Requirements for Pregnancy and

Lactation Labeling

Prescription Drug & Biologics Long-Term Actions

354 Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; Policies, Requirements, and

Administrative Procedures.

Claims in the News

Hello!

If you are tuned to news about regulatory issues you are likely aware of recent lawsuits being brought against companies for claims made on food products.  In one instance a mom in California is suing Nutella® over claims that the product is part of a healthy breakfast (http://www.foodnavigator-usa.com/Legislation/Nutella-manufacturer-faces-lawsuit-over-nutrition-claims). In another, the National Consumer League (NCL) has filed a complaint with the Federal Trade Commission alleging that the labeling and claims made on VitaminWater® product labels are “dangerously misleading” (http://www.foodproductdesign.com/news/2011/02/ncl-vitaminwater-ads-labels-are-dangerously-misle.aspx). This is not the first time complaints have been raised regarding VitaminWater® labeling.  Last year the Center for Science in the Public Interest (CSPI) filed suit claiming that the labeling of this product line included inappropriate nutrient content claims and further that the products were in violation of FDA fortification regulations.

These actions by groups and private citizens reveal a level of risk to companies making claims about their products that go beyond the typical risks from FDA and FTC that we regularly alert our clients to when reviewing their labels, brochures and websites.  It is rare that product labeling poses no risk and every company must determine the level of risk they are comfortable with.  It is common for companies to decide to push the envelope and take some risk since government enforcement actions are taken against only a small number of companies and while relabeling can be expensive, first offenses rarely result in fines.  Groups such as NCL and CSPI typically target large, high profile companies but the lawsuit by the private citizen against Nutella®, a product with a relatively small market share, made me sit up and take notice; particularly since the product does include nutrition information in compliance with FDA labeling regulations.  While the advertising tells the whole story—that Nutella® can be part of a healthy breakfast—the suit demonstrates that the consumer took only the highlight of the marketing message—healthy.  It will be interesting to see what happens with this case.  Will the standard that claims must be truthful, not misleading and supported by data have to be modified to account for consumers who do not listen to the whole message? 

While we cannot predict the outcome of these cases, we work to help our clients understand labeling regulations and the risks posed by the claims they make about their products.  We welcome your inquiries regarding claims, labeling and product development and hope to partner with you for your success.  Visit us at www.BioTransApp.com.

New FDA Update Blog

Hello!

For several years I have been sending occasional email updates on various FDA and sometimes USDA topics to clients of Bioscience Translation & Application (www.BioTransApp.com), a service of Cadman Consulting Services, LLC.  I frequently hear back that the information is helpful and I have decided to collect those messages in a blog.  I will also use this blog to comment on other regulatory issues that perhaps don't warrant an email.

I will be working to establish different pages for different regulatory sectors: Food, Dietary Supplements, Cosmetics, Medical Devices, Drugs, etc. so that you can easily find topics of interest.

I hope that you will find the information helpful and interesting!

Evelyn

FTC and Two Well-controlled Clinical Studies

In their settlement with Dannon over claims on DanActive and Activia, the FTC again evoked its standard of “two well-control clinical trials” to support structure function claims.  This standard was previously applied to Nestlé’s Boost® Kids Essentials drink and POM Wonderful Pomegranate Juice (POM is challenging FTC’s 2 clinical trial standard but the courts have yet to weigh in). 

FDA has written an extensive guidance document on claim substantiation without providing a definitive number of studies and instead relying on the interpretation of ‘adequate’ studies to support the claims.  FDA and FTC cooperate on cases involving claims on foods and supplements with FTC taking the lead in most cases.  Does this mean that FTC’s ‘two well-controlled clinical studies” will be the standard? Would ‘two well-controlled clinical studies’ prove to be a safe harbor for companies making structure function claims that do not directly or indirectly discuss disease states?  There’s just no telling but stay tuned.

The use of structure function claims on food products has been increasing and FDA is watching closely and cracking down on companies making claims with help from the FTC.  As a review, food products may include claims about the levels of nutrients that have an established RDI or DV as long as the levels of fat and sodium do not exceed set limits. They may also make certain health claims that link nutrients to disease prevention and ‘qualified’ health claims that have weaker support (see http://www.fda.gov/Food/LabelingNutrition/LabelClaims/HealthClaimsMeetingSignificantScientificAgreementSSA/default.htm)

and http://www.fda.gov/food/labelingnutrition/labelclaims/qualifiedhealthclaims/default.htm, respectively).

Food companies are getting into trouble when trying to make structure function claims. These claims discuss how the product or ingredients in it affect the normal, healthy structure or normal, healthy function of the body or its systems and do not discuss any drug-like properties or imply that the product in any way may prevent, treat, or cure any disease.  It is possible to craft claims that discuss the effects of the product on ‘normal’ conditions that are occasional, mild, temporary and self limiting such as occasional sleeplessness, occasional irregularity, and occasional indigestion.  All claims must be truthful, not misleading and backed by scientific evidence.

We at Bioscience Translation & Application stand ready to review your claims and supporting data and to help you craft appropriate claims and we welcome your inquires on these and other topics relating to food regulations. Learn more atwww.BioTransApp.com