US FDA issues guidance on Interim Product Reporting for Human Drug Compounding Outsourcing Facilities
US Food and Drug Administration (FDA) has issued a guidance on Interim Product Reporting for Human Drug Compounding Outsourcing Facilities under Section 503B of the Federal Food, Drug, and Cosmetic Act. The guidance is intended for outsourcing facilities that compound human drugs. Now the outsourcing facilities may elect to register with FDA under section 503B.
If an outsourcing facility registers, it must report to FDA information about the drugs compounded at the outsourcing facility. This guidance focuses on electronic submission of drug reporting information.
The Drugs Quality and Security Act (DQSA) adds new section 503B to the FD&C Act. Under section 503B(b), a compounder may elect to become an outsourcing facility by registering with FDA. Upon initially registering as an outsourcing facility, and twice each year which is once in June and once in December, an outsourcer that registers with FDA must submit to the Agency a report identifying the drugs compounded by the facility during the previous six-month period. For each identified drug, the outsourcing facility must provide certain information listed in section 503B(b).
An outsourcing facility can qualify for exemptions from the FDA approval requirements in section 505 of the FD&C Act by meeting the requirements described in the rest of section 503B. Outsourcing facilities will be inspected by FDA and must comply with other provisions of the FD&C Act, such as current good manufacturing practice (cGMP) requirements.
This guidance addresses the provisions in the DQSA regarding the drug reporting requirements for registered outsourcing facilities. A separate guidance provides instructions on how outsourcing facilities should register with FDA. This guidance provides instructions for interim reporting until FDA can modify its electronic submission system to accept the electronic reports 55 for drugs compounded by outsourcing facilities. When FDA has modified its current electronic system, we will issue a new outsourcing facility product reporting guidance describing the updated format for long-term use, stated the regulatory authority.
Under section 503B each registrant must submit a product report to FDA. This report must identify all drugs compounded by the outsourcing facility during the previous six-month period and provide information on each drug. This includes: active ingredient and strength of active ingredient per unit, source of the active ingredient, the National Drug Code (NDC) number of the source drug or bulk active ingredient, if available. The regulatory also insists information on the dosage form and route of administration, package description, number of individual units produced; and NDC number of the final product, if assigned.
FDA encourages companies wishing to compound as outsourcing facilities to register with it immediately. If a facility registers before June 2, 2014, FDA does not intend to immediately enforce the requirement to report product information at the time of initial registration, as long as the facility submits its report within two months after the date of that initial registration.
Section 503B(b)(3) of the FD&C Act requires outsourcing facilities to submit drug reporting information by electronic means unless the regulator grants a request for a waiver of such requirement.
Two devices aid in screening and diagnosis of cystic fibrosis
Today the U.S. Food and Drug Administration allowed marketing of four diagnostic devices that can be used for high throughput gene sequencing, often referred to as “next generation sequencing” (NGS). These instruments, reagents, and test systems allow labs to sequence a patient’s DNA (deoxyribonucleic acid).
The new technology also gives physicians the ability to take a broader look at their patients’ genetic makeup and can help in diagnosing disease or identifying the cause of symptoms.
“NGS is changing the way we look at genomics,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in FDA’s Center for Devices and Radiological Health. “Before NGS, sequencing genes associated with a particular disease was a long and costly process. Today, we have the capability to read and interpret large segments of DNA very quickly in a single test and this information-rich technology is becoming more accessible for use by physicians in the care of their patients.”
Two of the newly cleared devices are used to detect DNA changes in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which can result in cystic fibrosis (CF), an inherited chronic disease that affects the lungs, pancreas, liver, intestines, and other organs of those who inherit a faulty CFTR gene from both parents.
More than 10 million Americans are CF carriers and approximately 30,000 children and adults in the U.S. are affected with CF. Most children with CF are diagnosed by age 2 and the average life span for people with CF who live to adulthood is approximately 37 years.
The cleared devices include:
- The Illumina MiSeqDx Cystic Fibrosis 139-Variant Assay, which checks specific points in the patient’s CFTR gene sequence to detect known variants in the gene. Information about which DNA changes are associated with symptoms of cystic fibrosis is found in the Clinical and Functional TRanslation of CFTR database (CFTR2 ).
The Illumina MiSeqDx Cystic Fibrosis Clinical Sequencing Assay, which sequences a large portion of the CFTR gene to detect any difference in the CFTR gene compared to a reference CFTR gene.
Data submitted by Illumina for their cystic fibrosis tests included comparisons of the sequence results to Human Genome Build 19, a reference representation of the human genome. In addition, Illumina evaluated the performance of its instrument and reagent systems against a publically available quality-weighted human reference genome that was created through collaboration between the FDA and the National Institutes of Standards and Technology (NIST).
FDA authorized sequencing devices provide labs with quality and performance information
The FDA also granted de novo petitions for the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents, two devices that make up the first FDA-regulated test system that allows laboratories to develop and validate sequencing of any part of a patient’s genome. The Universal Kit reagents isolate and create copies of genes of interest obtained from patient blood samples, and the MiSeqDx platform analyzes the genes. The software compares the patient’s genomic sequence to a reference sequence and reports back any differences between the patient and the reference.
“The FDA’s review of the MiSeqDx and sequencer and Universal Kit reagents provides clinical laboratories with information about the expected performance of the device and the quality of the results,” said Dr. Gutierrez. “This information was not previously available for next generation sequencers, and, with this platform, labs can develop tests for clinical use with greater confidence because they use FDA authorized devices.”
The FDA reviewed the Illumina MiSeqDx instrument platform and the Illumina Universal Kit reagents through its de novo classification process, a regulatory pathway for some novel low-to-moderate risk medical devices that are not substantially equivalent to an already legally marketed device.
For the de novo petitions, the FDA based its decision on the demonstrated performance of the MiSeqDx instrument and Universal Kit reagent systems across numerous genomic segments spanning 19 human chromosomes.
Illumina MiSeqDx instrument platform, Universal Kit reagents, MiSeqDx Cystic Fibrosis 139-Variant Assay, and MiSeqDx Cystic Fibrosis Clinical Sequencing Assay are manufactured by Illumina, Inc. in San Diego, Calif.
Pharmaceutical industry wants the government to take immediate steps to clarify its stand on the proposed ban on the use of plastic and PET containers for liquid formulations. The government needs to substantiate with scientific evidence how the use of PET containers for packing liquid formulations will be harmful to the patients so that the industry will not be in a state of confusion.
This demand comes in the wake of growing concern within the industry over the Drugs Technical Advisory Board (DTAB) recommendation to the DCGI on phasing out of the use of plastic and PET (Polyethylene Terephthalate) containers for liquid formulations from the market on a gradual base. Goa Pharmaceutical Manufacturer’s Association (GPMA) pointed out that a lot of projects focused on expansion of oral liquid preparation have been stalled across the country due to the uncertainty and lack of clarity on the use of PET bottles.
They fear that lack of timely intervention from the government in clarifying the matter will affect not only the business but also lead to severe shortage of paediatric preparations, formulations meant for geriatrics, women in reproductive age group and pregnant women which comes in PET containers. According to A K Burman, president, GPMA globally PET is used as a well expected packaging material, even in the regulated markets like US, UK Japan etc. He stressed that industry finds it a little confusing on why India needs to suddenly ban the use of PET especially in the absence of any scientific evidence support the ban.
“Expansion plans largely depend on its packaging aspect, thus the government should come forth with a proper explanation based on scientific data on an urgent basis. So as to ensure that no one suffers due to time lapse. We fear that if this issues is not addressed at the earliest in the long run , the patients may feel the brunt of the same,” he cautioned.