Tag Archive for: FDA

FDA Publishes New Draft Guidance on Biosimilars As Congress Raises Questions About FDA’s Use of Draft Guidance Documents

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As we previously reported here, here, and here, the U.S. Food and Drug Administration (“FDA”) has been drafting guidance regarding the regulation of biosimilars since as early as 2011. A biological product is biosimilar if it is “highly similar to the reference product notwithstanding minor differences in clinically inactive components” and if there are “no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” See section 351(i)(2) of the PHS Act here. The biosimilar approval process is an abbreviated pathway for FDA licensure of biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-licensed reference product under the Biologics Price Competition and Innovation Act (“BPCIA”).

In 2012, the FDA released three guidance documents, which outlined its expectations for submitting applications for biosimilar products to FDA pursuant to the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”). Together, these three draft guidances provided industry with general questions and answers regarding the implementation of BPCIA, as well as scientific and quality considerations for demonstrating biosimilarity to a reference product. The following year, the FDA released a fourth draft guidance document outlining the procedures for formal meetings that occur between the FDA and sponsors or applicants during the development phase of a biosimilars. Since then, manufacturers of biological products have eagerly anticipated the FDA’s release of final guidance.

On May 14, 2014, instead of issuing final guidance on biosimilars, the FDA issued yet another draft guidance document, Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product. According to the FDA, this draft guidance is “intended to assist biological product sponsors with the design and use of clinical pharmacology studies to support a showing that a proposed therapeutic biological product is ‘biosimilar’ to its reference product under [BPCIA].” This draft guidance specifically applies to products for which pharmacokinetic (“PK”) and pharmacodynamic (“PD”) data are required to help demonstrate biosimilarity.

Summary of FDA’s Draft Guidance on Clinical Pharmacology Data to Support a Demonstration of Biosimilarity

Although the information set forth in the FDA’s newest draft guidance is extensive, much of the information covered here was previously addressed in the draft guidances issued in 2012 and 2013.  Unfortunately for industry, the FDA’s newest draft guidance does not offer much insight into the FDA’s regulation of biosimilars, the specific requirements for submitting a biosimilar application (“§351(k) application”), nor the likelihood of success of obtaining approval through this pathway. (For coverage of the FDA’s recent draft guidance, please click here, here, and here.)

Similar to the draft guidances issued by the FDA in 2012, FDA’s 2014 guidance explains the step-wise process for demonstrating biosimilarity. This draft guidance emphasizes the “critical” role of pharmacological studies in the demonstration of biosimilarity because they “support[] a demonstration that there are no clinically meaningful differences between the proposed biosimilar and the reference product.” Moreover, clinical pharmacology studies are important because they “add to the totality of the evidence, reduce residual uncertainty, and thus guide the need for and design of subsequent clinical testing” in the overall demonstration of biosimilarity. Id. When developing proposed biosimilar products, the FDA identified three key concepts that must be addressed in any §351(k) application: (1) exposure and response assessment, (2) evaluation of residual uncertainty, and (3) assumptions about analytical quality and similarity.

–          Exposure and Response Assessment: The FDA explains that exposure-response information is important for determining the “safety, purity, and potency of any biological product.” For the purposes of this guidance document, exposure refers to PK variables, including input of all active components of a biological product as measured by dose and drug concentrations in plasma and other biological fluids. Response, on the other hand, refers to PD variables, or the direct measures of the pharmacological or toxicological effects of a drug on the body.

–          Evaluation of Residual Uncertainty: The FDA intends to use a risk-based approach in evaluating the data provided in a sponsor’s § 351(k) application. Specifically, the FDA announced that it will consider the “totality of the data and information submitted,” including data from structural and functional characterization, nonclinical evaluations, human PK and PD studies, clinical immunogenicity testing, and investigation of clinical safety and clinical effectiveness.

–          Assumptions About Analytical Quality and Similarity: The FDA directs sponsors to conduct “extensive and robust comparative structural and functional studies (e.g. bioassays, binding assays, and studies of enzyme kinetics)” to evaluate whether the proposed biosimilar and the reference product are highly similar. The capabilities and limitations of these “state-of-the-art analytical assays” should be fully described in the § 351(k) application’s analytical assessment. Interestingly, the FDA encourages applicants to compare the quality attributes of the proposed biosimilar product with those of the reference product using a “meaningful fingerprint-like analysis algorithm” that “covers a large number of product attributes and their combinations with high sensitivity using orthogonal methods.” In using this “fingerprint-like analysis algorithm,” the FDA expects sponsors to reach one of four assessments about their product: not similar, similar, highly similar, and highly similar with fingerprint-like similarity. “Not similar” products are not recommended for the biosimilar pathway unless, for example, modifications are made to the manufacturing process that are likely to lead to a highly similar biological product. “Similar” products require additional data or studies to determine if the differences are acceptable to consider the proposed product as highly similar to the reference product. Proposed biosimilars that are “highly similar” and “highly similar with fingerprint-like similarity” permit high or very high confidence that the proposed product meets the statutory standard for biosimilarity and allow sponsors to “conduct targeted and selective animal and/or clinical studies to resolve residual uncertainty and support a demonstration of biosimilarity.”

Furthermore, the FDA explains that using “accurate, precise, specific, sensitive, and reproducible” bioanalytical methods of evaluating PK and PD properties of a proposed biosimilar and its reference product is “critical” to evaluating clinical pharmacology similarity. The draft guidance document goes on to detail the requirements for these data types, including specific information regarding ligand binding assays, concentration and activity assays, and pharmacodynamics assays that should be included in an application. In addition to these bioanalytical evaluations, the FDA recommends that applicants collect safety and immunogenicity data to supplement the overall assessment of biosimilarity.

Lastly, the guidance document encourages applicants to discuss crucial aspects of their clinical pharmacology development plan with the FDA. Specifically, the draft guidance outlines nine different study design areas that industry should consider in those discussions: crossover design, parallel design, the reference product, study population, dose selection, route of administration, pharmacokinetic measures, pharmacodynamic time profile, and the statistical comparison of PK and PD results.

The FDA is accepting comments on this draft guidance until the August 12, 2014. Comments can be submitted electronically to http://www.regulations.gov [Docket No. FDA-2014-D-0234].

FDA Under Scrutiny for Draft Guidances

In its 2014 biosimilars draft guidance, the FDA reiterates that, once finalized, this guidance will be a part of a series of guidance documents intended to implement the BPCIA. It will be interesting to observe how swiftly the FDA issues final guidance on biosimilars, especially in light of the recent scrutiny the FDA has faced regarding its policies on and use of draft guidances. One week before the most recent draft guidance was issued, the FDA received a letter from the U.S. Senate Committee on Health, Education, Labor and Pensions (the “Senate HELP Committee”), expressing “significant concern about the [FDA’s] use of draft guidances to make substantive policy changes.” (The full text of the Senate HELP Committee’s letter to FDA can be accessed here, courtesy of Hyman, Phelps, & McNamara, P.C.) In its letter to FDA, the Senate HELP Committee voiced its concern that “that these draft guidances are not being revised, finalized, or withdrawn in a timely manner.” As a result of the FDA’s failure to finalize guidances in a timely manner, FDA review staff, patients, clinicians, and FDA-regulated companies “feel compelled to follow draft guidances as if they were final” because these drafts are the only information available on the agency’s most current thinking on important issues.

Furthermore, the Senate HELP Committee expressed concern that the FDA “issues guidance that seemingly does not take into account, or may even conflict with, the scientific community.” In order to better understand the FDA’s use of guidance to effectively communicate with FDA-regulated entities seeking advice on how to bring life-saving medical products to patients, the Senate HELP Committee has requested FDA to provide additional information about all Level 1 Draft Guidances, including the date issued, and the timeline with which the FDA plans to withdraw, revise, or finalize each guidance. The Senate HELP Committee also requested the FDA to provide an update on FDA-wide activities to implement the “best practices” to make the finalization of guidance more efficient and expeditious. In addition, the letter asked the FDA to produce information on the average amount of time that FDA has taken to finalize draft guidances in the last five years, and to explain how it ensures that FDA staff does not follow the guidance in the absence of any other policy or final guidance.

Conclusion

Given that the FDA is operating under the Senate’s microscope, it is difficult to speculate exactly when industry should expect the FDA to publish final guidance on biosimilars. It remains to be seen whether issuing the recent draft guidance shortens FDA’s timeframe for releasing final guidance or tolls FDA action in asking for public comment. The attorneys at Fuerst Ittleman David & Joseph, PL will continue to monitor any developments in the FDA’s regulation of biosimilars. For more information, please feel free to contact us by email at contact@fidjlaw.com or by phone at (305) 350-5690.

FDA Announces Public Meeting on Approval Pathways for Biosimilars

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The U.S. Food and Drug Administration (FDA) has announced that it will hold a two-day public hearing on November 2-3, 2010 for the purpose of gathering “input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).”

The Patient Protection and Affordable Care Act (Pub. L. 111-148), signed into law by President Obama in March of this year, contains the BPCI Act. The BPCI Act amends the Public Health Service Act (PHS Act) to create an abbreviated approval pathway for biological products. In order to take advantage of this abbreviated pathway, these biological products must be shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.

Biosimilarity may be demonstrated through the use of scientific support (clinical trials, animal studies, etc.) with the appropriate number of trials and appropriate types of studies. The appropriate number and type required will be determined by the FDA. For a product to be considered biosimilar, data collected from the requisite study/studies must show that the biological product is “highly similar to the reference product, notwithstanding minor differences in clinically inactive components.” While it is unclear what level of clinical similarity is required to reach the finding of “highly similar”, The Agency intends to address this issue during the November hearing.

For more information on biologics or the BPCI Act, contact us at contact@fidjlaw.com.

FDA Busy Crafting Calorie Court Regulations

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The FDA has begun the process of establishing regulations to implement recent federal law that mandates calorie information be posted at many chain restaurants and vending machines throughout the United States. The mandate was signed into law on March 23, 2010, as part of the Patient Protection and Affordable Care Act, (“PPACA”) and requires that all restaurants with 20 or more locations post calorie counts of their products on menus, menu boards, and drive-through menus. Other nutritional information, including amounts of sodium, saturated fats and cholesterol must be made available to consumers in written form upon request. Additionally, all chain restaurants must include on their menus the Secretary of the Department of Health and Human Services statement on suggested daily calorie intake.

The PPACA requires chain restaurants to label the calorie content for standard menu items and self-service foods, such as buffets and salad bars. However, foods that are daily specials, limited-time offerings, or seasonal items are exempt from the calorie count legislation. Also, vending machines must display calorie disclosures for each item offered for sale unless the Nutritional Facts panel for a food is available for the customer to view prior to purchasing.

The federal calorie count legislation is intended to create a uniform national policy on nutritional information available on chain restaurant menus. PPACA is similar in design and purpose to several state laws and local ordinances requiring calorie count displays at chain restaurants. New York City currently has such a calorie count display law in effect. The National Restaurant Association supported the implementation of a federal guideline as an alternative to numerous labeling schemes that could vary from state to state.

The FDA has until March 2011, one year from the passage of the PPACA, to develop and implement regulations to enforce the calorie count mandate. Once implemented, the FDA will be in charge of enforcement and penalties for violations. On July 7, 2010, the FDA began receiving public comments on how to implement section 4205 of the PPACA. The comment period runs for 60 days and will close on September 5, 2010.

For more information regarding current FDA authority, procedure, or regulations please contact us at contact@fidjlaw.com.

Drug Recalls Increase 309% in 2009

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August 19, 2010

The U.S. Food and Drug Administration (FDA) reported more than 1,742 prescription and over-the-counter (OTC) drug recalls in 2009. That number is a huge increase from the 426 recalls reported in 2008 and the 391 recalls reported in 2007. With the spike in the number of drug product recalls, product and manufacturing quality is being called into question in the media and in the public.

Recalls are actions taken by a drug manufacturer, repackager, or distributor to remove a drug from the market. Recalls may be conducted on a firm’s own initiative, by FDA request, or by FDA order under statutory authority. The FDA publishes information regarding recalls, market withdrawals, and safety alerts here.

The increase in drug recalls has continued into 2010 with 296 recalls reported in the months of January through June. This rapid increase in drug recalls likely prompted two bills that have been introduced this year in Congress that would impose stricter regulations on the drug industry (see here and here). The bills would also give the FDA authority to mandate drug recalls.

Recent recalls of drug products by Tylenol and McNeil Consumer Healthcare, a Johnson & Johnson unit, (see here and here) have brought concerns regarding manufacturing and product quality to the publics attention. The quality of raw materials used in manufacture as well as contamination and faulty labeling and packaging could be to blame for the lack of manufacturing quality. This lapse in quality could be credited to the fierce competition in the drug manufacturing industry. Drugmakers are cutting costs and cutting back on manufacturing investments to stay competitive.

The generic drug market also fuels the competition in the industry. Generic drugs muake up approximately 75% of all prescription drug sales. The rush by generic drug manufacturers to be the first to market a generic version of a drug after the drug loses patent protection can create a deficit in manufacturing quality.

Advantage Dose, a drug repackager, accounted for more than 1,000 of the reported recalls in 2009. Repackagers that relabel drugs into smaller resale units have also drawn attention for increased recalls due to flawed labeling and packaging.

In an industry that is already rife with competition, drugmakers must be conscientious of quality control. In light of the new attention given to manufacturing quality by the public, policy makers and the media, drugmakers, more than ever, must ensure they are producing compliant, quality products.

For information on how Fuerst Ittleman, PL can help your company with issues surrounding drug manufacturing, repackaging, importing, and distribution, contact us at contact@fidjlaw.com.

Senate Bill Introduced to Increase FDA Authority

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August 5, 2010

This week Sen. Michael Bennet (D-CO) introduced the Drug Safety and Accountability Act of 2010 to the U.S. Senate. The Bill aims to increase the authority of the U.S Food and Drug Administration (FDA) to regulate drugs manufactured overseas and allow for heightened oversight and regulation of over-the-counter (OTC) drugs.

Bennets Press Release explains, “For too long, the FDA has lacked the proper authority to adequately safeguard our drug supply and protect Colorado consumers. Its time Washington took acting to ensure the medicines Coloradans rely on are safe, and that those entrusted with the responsibility of developing these drugs are equipped to keep consumers out of harms way.”

The Bill was introduced the same day the Pew Prescription Project released poll results indicating that nine in ten voters support new safety measures for prescription drugs. The report also revealed that U.S. consumers have low confidence in the safety of drugs manufactured abroad, especially those produced in China and India.

The FDA has indicated support for the reforms, with Principal Deputy Commissioner Joshua Shafterstein stating that he believes the FDA needs authority to issue mandatory drug recalls. Additionally, The Pew Prescription, AARP, American College of Physicians, Consumers Union, Society of Chemical Manufacturers and Affiliates, the Community Catalyst, and others have issued a joint letter to Congress in support of the Bill. Proponents of the Bill estimate that 80% of active ingredients in U.S. pharmaceuticals are made abroad. Proponents, including the Bills sponsor, also note the 1,742 drug recalls implemented in 2009, which represents a 400 percent increase over 2008.

The new Bill would provide the FDA with additional recall power and enforcement options along with better tools to look into possible drug quality and safety issues including:
¢ Authority to assess civil penalties for Food, Drug and Cosmetic Act violations.
¢ Authority to subpoena documents and witnesses.
¢ Increased ability to exchange information between the FDA and other regulatory agencies.
¢ Ability to protect industry whistleblowers who bring information to the FDA.

The Bill would also increase manufacturer standards by:
¢ Requiring Companies to institute quality management plans to insure quality and safety of their drug components.
¢ Requiring companies to increase supplier oversight and document entities involved in supply chain for drug manufacturing

Finally, the Bill aims to increase oversight of over-the-counter medications by re-assigning them from a lower-risk category for inspection.

This Senate Bill comes only two weeks after House Representative Ed Towns (D-NY), Chair of Committee on Government Oversight and Reform, introduced the FDA Mandatory Recall Bill, also intended to increase FDA power. The House Bill, introduced July 15, would allow for the FDA to implement a quicker and more thorough recall process than the voluntary recall process currently in place. If the House Bill passes, the FDA will have the ability to order mandatory recalls for adulterated or misbranded drugs or drugs which pose a considerable risk of death or serious health consequences. The Bill was referred to the House Committee on Energy & Commerce.

The House Bill was introduced the same day Johnson & Johnson submitted a plan to correct problems at a Tylenol plant. The plan was required by the FDA after an April 30th cite check found numerous violations of good manufacturing conditions. The cite check coincided with recalls issued for Benadryl, Motrin, Tylenol, and Zyrtec for infants and children because of possible metallic particle contamination. The plan included new equipment and operations procedures.

For more information regarding current FDA authority, procedure, or regulations please contact us at contact@fidjlaw.com.

Feds Challenge Stem-Cell Treatment

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WASHINGTON (CN) – The Department of Justice says a stem-cell treatment to rebuild hips, knees and other joints has been misbranded by its manufacturer, Regenerative Sciences, and violates standards of the federal Food, Drug, and Cosmetic Act.

Colorado-based Regenerative Sciences calls the cultured stem cells used in the company’s Regenexx procedure a “cultured cell product,” while the FDA claims the cell product should be considered a drug. The Regenexx procedure involves taking cells from a patient’s bone marrow, processing the cells with the patient’s blood, then reinjecting the “product” into the patient.

The cultured cells should be classified as a drug, the government says, as they end up in a syringe to be injected back into the patient.

“Defendant’s cultured cell product is a ‘drug’ within the meaning of the FDCA, because Defendant’s labeling and promotional literature, including information contained on Regenerative Sciences’ website, establish that their cultured cell product is intended to be used in the cure, mitigation, and treatment of diseases in man and to affect the structure and function of the body,” says the government in its complaint.

Dr. Christopher Centeno, Regenerative Sciences’ acting CEO and defendant in the case, disputes the FDA’s claims that the product is a drug.

“This is about patients. We don’t dislike [the FDA] and respect its authority over drug production. However, we also believe a physician has the right to use stem cells or other body parts to help heal the patient, especially when it’s a better alternative to more invasive procedures,” says Dr. Centeno.

He says making a patient’s own stem cells a drug “won’t add measurable safety, but it will hugely increase cost and delay helping patients find better options for their medical problems.”

According to the FDA, if the cultured cell product is a drug, then Regenerative Sciences is not following the guidelines of “current good manufacturing practice.” The agency says its nearly two-month investigation of the company’s Colorado facilities “showed that the methods used in, and the facilities and controls used for, the manufacture, processing, packing, or holding of the cultured cell product do not conform to and are not operated or administered in conformity with current good manufacturing practice.”

Among the violations, the FDA says, Regenerative Sciences failed “to perform appropriate laboratory testing of each batch of drug product required to be free of objectionable microorganisms.”

The government says the company promised to correct some violations, “but they refused to correct many others because they do not believe that Regenerative Sciences is a drug manufacturer.”

“Regenerative Sciences has had an exemplary safety record, showing that our procedure is far safer than the knee replacements it has helped patients avoid,” Centeno says.

The company has sued the FDA four times in two years, trying to get a decision that the cultured cell product is “the practice of medicine” and not a drug, he explained in an interview with Courthouse News.

Colorado Medical Clinic Welcomes Opportunity to Fight FDA in Court

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Clinic Claims FDA Has Repeatedly Overstepped Regulatory Authority

DENVER, Aug. 9 /PRNewswire/ — Regenerative Sciences, Inc., a Colorado medical practice that specializes in the use of a person’s own stem cells to help patients avoid more invasive orthopedic surgery, announced today that the US Food and Drug Administration (FDA) is seeking to enjoin the clinic physicians from practicing medicine using patients’ own stem cells. The lawsuit will allow Regenerative Sciences to question the FDA’s policy that adult stem cells can be classified as drugs when used as part of a medical practice.

“The FDA will finally answer our questions, in court, about their claims and jurisdiction as opposed to doing everything in their power to avoid the issue that we are not a drug manufacturer, but simply a medical practice,” said Christopher Centeno, M.D., Regenerative Sciences’ medical director.

The FDA claims that Regenerative Sciences is using an “adulterated” product because it fails to follow mass manufacture guidelines in its medical practice that is applied to drug factories producing millions of doses. Rather than mass producing drugs, Regenerative Sciences uses the patient’s own stem cells to treat common orthopedic problems. Regenerative Sciences has had an unblemished safety record, recently publishing a large study showing that its procedure is dramatically safer than the traditional surgical procedures it has helped many patients avoid. Regenerative Science’s lab has strictly adhered to the International Cellular Medicine Society’s (ICMS) strict, professional guidelines and has been audited three times by independent third parties with no serious safety concerns.

“ICMS lab guidelines are the best fit for autologous cell processing and provide strong patient protection. If the FDA had any valid concerns about our medical practice not using drug factory guidelines, they knew about that in Spring of 2009 and did nothing. They did nothing because there were no safety issues. Their focus on this now is litigation posturing,” stated Centeno.

Regenerative Sciences has been using its patients’ stem cells to treat orthopedic conditions since 2005 and received an untitled letter from the FDA in 2008 claiming its medical procedure was creating a new biologic drug. The FDA inspected Regenerative Science’s facility in 2009, and found, at that time, that it was not compliant with drug mass manufacture guidelines, but failed to take any action.

Regenerative Sciences has filed two lawsuits against the FDA in an effort to force the organization to respond to questions about their jurisdiction in the matter. The medical practice filed a suit in Denver District Court in 2008 based on the issue that the FDA regulations regarding creating a drug out of the patient’s own stem cells exceeded the FDA’s congressional authority and that the Food, Drug, and Cosmetic Act contains exemptions for physicians using innovative therapies that do not go through FDA approval as part of their medical practice. Last month, Regenerative Sciences was forced to file suit against the FDA again, this time seeking a Temporary Restraining Order (TRO) to prompt the FDA to take “final agency action” or leave its medical practice alone following an exhaustive inspection of Regenerative Science’s facilities and taking no action.

“For two years we’ve been prodding the FDA to respond to our questions about how it has the ability to regulate a medical practice, so we’re encouraged that, as a result of this recent suit, the courts will decide if it the FDA has regulatory authority over the adult stem cells that live in everyone’s body,” stated Centeno. “This is an important case for everyone that suffers from any type of illness, not just patients with orthopedic problems. It will decide, once and for all, if the government has the right to restrict a patient and their doctor from using a person’s own stem cells to treat disease. Regenerative Sciences believes that stem cells are body parts and not the property of the government or big pharma.”

Adult stem cells are those found throughout the patient’s body. Recent medical research has indicated these important cells have as much clinical promise as the more controversial embryonic stem cells (cells taken from an embryo).

“What we’re doing in our Colorado medical practice is no different, in principle, than a fertility clinic that uses the in-vitro fertilization technique. The only difference is that we’re using stem cells and fertility clinics use fertilized eggs,” stated John Schultz, M.D., one of the founders of the Centeno-Schultz Clinic.

The FDA’s lawsuit is being closely monitored by the International Cellular Medicine Society (ICMS), a global nonprofit dedicated to patient safety and education in the medical use of adult stem cells that represents over 1,000 physicians, researchers and patients from over 35 countries on 6 continents. ICMS executive director, David Audley, stated “The Centeno-Schultz Clinic meets our strict criteria for the safe therapeutic use of adult autologous stem cells. There is more medical and scientific evidence supporting this type of medical therapy for orthopedic conditions, for example, than there is for many approved drugs that the FDA allows to be used in off-label or unconventional applications.”

About Regenerative Sciences

Headquartered in Colorado, Regenerative Sciences, Inc. is an extension of the medical practice of the Centeno-Schultz clinic and is focused on the development of the Regenexx┞¢ procedure, a breakthrough non-surgical option for people suffering from various orthopedic disorders. The physicians at Regenerative Sciences have developed a patent-pending procedure that uses a person’s own stem cells and blood growth factors to help regenerate bone and cartilage. Regenerative Sciences believes in educating patients, providing choices, offering options and encouraging people to take an active role in their own treatment. More information can be found at http://www.regenexx.com

SOURCE Regenerative Sciences, Inc.

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FDA Seeks Comment on Draft Guidance for Industry, Third Parties and FDA Staff; Medical Device ISO 13485:2003 Voluntary Audit Report Submission Program

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This week, United States Food and Drug Administration announced that a new draft guidance, “Medical Device ISO 13485:2003 Voluntary Audit Report Submission Program,” is available for public review and comment.  This new FDA program allows for a medical device manufacturer whose facility is inspected and audited by any of the Global Harmonization Task Force (GHTF) approved systems, like the Canadian Medical Devices Conformity Assessment System or European Union Notified Body, to voluntarily submit the results of that audit to the FDA.  The FDA will then utilize the results of that audit in its risk-based analysis of whether it can remove the firm from its work plan for the next year.  In other words, the FDA will use the audit conducted by the other accredited body to make decisions about which firms it will inspect during the upcoming year.  The Agency will base its decisions on the probability of risk reported in the audit and the type of device manufactured by the firm.  This is a way in which a compliant device manufacturer already audited through another recognized system may avoid an inspection by FDA.  The program benefits FDA, as well, as the program allows the Agency to use its resources to focus on auditing firms that require more oversight.

The International Organization for Standardization (ISO) is a group with representatives from various national standards organizations that promulgates worldwide proprietary industrial and commercial standards.  The medical device ISO 13485:2003 provides quality management system requirements for medical device manufacturers and distributors.  Under this ISO, a firm must demonstrate that it can produce medical devices and related services that are consistently compliant with the regulatory requirements set forth by ISO. The FDA, through the new draft guidance, will use the medical device ISO 13485:2003 to leverage audits performed by other GHTF regulators to assist the Agency in setting risk-based inspectional priorities.

The FDA is utilizing inspections and audits conducted by third parties and other regulators with increasing frequency.  The Agency is employing reliable reports from other regulatory bodies to establish a more efficient work plan.  Under the Medical Device User Fee Modernization Act of 2002 (MDUFMA), the FDA is authorized to train and accredit third parties to perform inspections of eligible establishments that manufacture Class II or Class III devices.  This voluntary program is known as the Accredited Persons AP for Inspections program.  While all firms remain subject to inspection by FDA, eligible manufacturers have the option of requesting inspection by an AP.  Additionally, in 2006, the FDA and Health Canada (HC) announced a pilot multi-purpose audit program (PMAP) allowing qualified accredited persons and auditing organizations under the AP for Inspections program and HCs equivalent program, the Third Party Auditing Organizations, to perform a single inspection that both FDA and HC can use.  The purpose of this pilot program is to evaluate the effectiveness of performing one third party inspection of a medical device firms quality system that would meet the regulatory requirements of both countries.  The pilot PMAP and FDAs new draft guidance evidence the Agencys movement toward recognizing the necessity of comity between international regulatory bodies regarding medical device firm inspections and audits.

Fuerst Ittleman, PL is experienced in handling the compliance matters of medical device manufacturers and distributors.  We also assist pharmaceutical and biotechnology firms with regulatory compliance and import/export requirements.  Please feel free to contact us at contact@fidjlaw.com to discover how we can help your company with medical device manufacture, inspections, importation/exportation, and distribution.

See 75 FR 28257.