Showing posts with label Drug Inspections. Show all posts
Showing posts with label Drug Inspections. Show all posts

Saturday, January 5, 2013

North Carolina Board of Pharmacy Steps Up Inspections of Compounding Pharmacies

Inspections of Compounding Pharmacies
Stepped Up
Board staff has stepped up inspections of North Carolina
pharmacies that specialize in compounding to ensure compliance with relevant law. In addition, Board staff is collecting
information from out-of-state pharmacies permitted in North
Carolina that specialize in compounding for the same purpose.
Already, Board inspectors have noted another uptick in the
compounding of “over-the-counter” drugs for general resale.
This is not a legal practice. This activity was the subject of
a lengthy item in the April 2008 Newsletter: www.ncbop.org/
Newsletters/Apr2008.pdf. Given the clarity of the law and
Board staff’s repeated emphasis on this issue, instances of this
practice will no longer be treated as an “educational” matter.
They will be treated as a disciplinary matter.

Quotation found in Jan. 2013 North Carolina Board of Pharmacy Newsletter found here

Tuesday, August 14, 2012

FDA Has Conducted More Foreign Inspections and Begun to Improve Its Information on Foreign Establishments, but More Progress Is Needed: GAO-10-961:


GAO-10-961: 

GAO Highlights: 

Highlights of GAO-10-961, a report to the Committee on Oversight and 
Government Reform, House of Representatives. 

Why GAO Did This Study: 

Globalization has placed increasing demands on the Food and Drug 
Administration (FDA), an agency within the Department of Health and 
Human Services (HHS), in ensuring the safety and effectiveness of 
drugs marketed in the United States. Drugs manufactured in more than 
100 countries were offered for entry into the United States in fiscal 
year 2009. FDA inspects drug manufacturing establishments in order to 
ensure that the safety and quality of drugs are not jeopardized by 
poor manufacturing practices. 

In 1998 GAO identified weaknesses in FDA’s foreign drug inspection 
program. In 2008 GAO found, among other things, that from fiscal years 
2002 through 2007, FDA inspected relatively few foreign establishments 
each year. GAO also determined that, because of inaccurate information 
in its databases, FDA did not know how many foreign drug 
establishments were subject to inspection. 

In 2008 GAO recommended that FDA increase inspections of foreign drug 
establishments and improve information it receives to manage the 
foreign drug inspection program. This report examines FDA’s progress 
since 2008 in (1) conducting more foreign drug inspections, and (2) 
improving its information on foreign drug establishments. GAO analyzed 
information from FDA databases, reviewed documents related to FDA’s 
efforts to both improve these databases and supplement its existing 
information on foreign drug establishments, examined staffing and 
funding information, and interviewed FDA officials. 

What GAO Found: 

FDA increased the number of foreign drug inspections it conducted from 
fiscal year 2007 to 2009, but still conducts relatively fewer foreign 
drug inspections each year than it conducts domestically. In fiscal 
year 2009, FDA conducted 424 foreign inspections, compared to 333 and 
324 inspections conducted in fiscal years 2007 and 2008, respectively. 
Using a list FDA developed to prioritize foreign establishments for 
inspection, GAO estimated that FDA inspected 11 percent of foreign 
establishments on this list in fiscal year 2009. At this rate, GAO 
estimated it would take FDA about 9 years to inspect all 
establishments on this list once. In contrast, in that same year, FDA 
conducted 1,015 domestic inspections, inspecting approximately 40 
percent of domestic establishments. GAO estimated that at this rate 
FDA inspects domestic establishments approximately once every 2.5 
years. Further, FDA’s approach in selecting establishments for 
inspection is inconsistent with GAO’s 2008 recommendation that FDA 
inspect, at a comparable frequency, those establishments that are 
identified as having the greatest public health risk potential if they 
experience a manufacturing defect, regardless of whether they are a 
foreign or domestic establishment. Instead, its foreign inspections 
continue to be driven by the establishments listed on an application 
for a new drug, instead of those already producing drugs for the U.S. 
market. 

FDA is taking steps to improve the information it receives from the 
drug establishment registration and import databases the agency uses 
to manage its foreign drug inspection program. For example, FDA is 
working to obtain more accurate information for its database that 
contains information about foreign establishments registered to market 
their drugs in the United States. In addition, FDA has an initiative 
underway to eliminate duplicate information from its database 
containing information about foreign establishments whose drugs are 
offered for import into the United States. However, these efforts are 
in the early stages. In addition, FDA is exploring other options for 
obtaining better information about foreign drug establishments, such 
as by collaborating with foreign regulatory authorities to exchange 
information about planned inspections and the results of completed 
inspections. 

In 1998, and again in 2008, GAO reported that FDA needed to conduct 
more inspections of foreign establishments and that it was vital that 
the agency strengthen the data it uses to manage its foreign drug 
inspection program. FDA has begun to respond to GAO’s recommendations; 
however, it has not yet fully addressed these weaknesses at a time 
when the volume of imported drugs and the number of foreign 
establishments producing these drugs have been increasing. Given the 
long-standing nature of these challenges and the nation’s reliance on 
drugs manufactured overseas, it is urgent that FDA implement GAO’s 
prior recommendations to better protect public health. HHS reviewed a 
draft of this report and agreed that more progress is needed in order 
to meet the challenge of safeguarding the nation’s drug supply in 
today’s global marketplace. 
To read the remainder of the report, click here.

Wednesday, June 27, 2012

FDA Guidelines Regarding Drug Inspections

The FDA website contains the following guidance regarding drug inspections:

5.5 - DRUGS

 5.5.1 - DRUG INSPECTIONS

Authority for inspection is discussed in IOM 2.2FD&C Act Sections 501(a)-(d) [21 U.S.C. 351(a)-(d)] describe the ways in which a drug may be or may become adulterated. Section 502 of the FD&C Act [21 U.S.C. 352] does the same, with respect to misbranding. Section 505 of the FD&C Act [21 U.S.C. 355] requires that new drugs be approved by FDA. Therefore, the purposes of a drug inspection are:
  1. To evaluate a firm's adherence to the concepts of sanitation and good manufacturing practice; i.e.,production and control procedures include all reasonable precautions to ensure the identity, strength, quality, and purity of the finished products;
  2. To identify deficiencies that could lead to the manufacturing and distribution of products in violation of the Act, e.g., non-conformance with Official Compendia, super/sub potency, substitution;
  3. To determine whether a firm is distributing drugs that lack required FDA approval including counterfeit or diverted drugs;
  4. To obtain correction of those deficiencies;
  5. To determine if new drugs are manufactured by the same procedures and formulations as specified in the New Drug Application documents;
  6. To determine the drug labeling and promotional practices of the firm;
  7. To assure the firm is reporting NDA field alerts as required by 21 CFR 314.81 and Biological Product Deviation Reports (BPDRs) for therapeutic biological products as required by 21 CFR 600.14;
  8. To determine if the firm is complying with the requirements of the Prescription Drug Marketing Act (PDMA) and regulations; and
  9. To determine the disposition of Drug Quality Reports (DQRS) received from the Division of Compliance Risk Management and Surveillance/CDER; and
  10. To determine if the firm is complying with postmarket Adverse Drug Experience reporting requirements as required by 21 CFR sections 310.305 (prescription drugs without approved NDA/ANDA), 314.80, 314.98, and 314.540 (application drug products), and 600.80 (therapeutic biological products), and Section 760 of the FD&C Act (non-application nonprescription products) [21 U.S.C. 379aa].

 5.5.1.1 - Preparation and References

Become familiar with current programs related to drugs. Determine the nature of the assignment, i.e., a specific drug problem or a routine inspection, and if necessary, consult other district personnel, such as chemists, microbiologists, etc., or center personnel, such as office of compliance staff. Review the district files of the firm to be inspected including:
  1. Establishment Inspection Reports,
  2. District Profiles,
  3. OTC monographs and other pertinent references for non-application products,
  4. Drug Applications (New, Abbreviated and Investigational) and the Knowledge Transfer Memo, if the Center has provided it for a specific pre-approval inspection,
  5. Therapeutic Biologics License Applications,
  6. Sample results,
  7. Complaints and Recalls,
  8. Regulatory files,
  9. Drug Quality Reports (DQRs), NDA Field Alert Reports (FARs), and Biological Product Deviation Reports (BPDRs)
  10. Drug Registration and Listing 
During this review identify products which:
  1. Are difficult to manufacture,
  2. Require special tests or assays, or can not be assayed,
  3. Require special processes or equipment, and
  4. Are new drugs and/or potent low dosage drugs.
  5. Begin Changed TextAre misbranded, unapproved, fraudulent, or compounded drugs containing ingredients that have been withdrawn or removed from the market for safety reasons.End Changed Text
Review the factory jacket, FACTS OEI and registration/listing data, and all complaint reports which are marked follow-up next inspection. These complaints are to be investigated during the inspection and discussed with management. See IOM 5.2.7.
Become familiar with current regulations and programs relating to drugs, CP 7356.002, et al. When making GMP inspections, discuss with your supervisor the advisability of using a microbiologist, analyst, engineer, or other technical personnel to aid in evaluating those areas of the firm germane to their expertise. Review the FD&C Act, Chapter V, Drugs and Devices. Review parts of 21 CFR 210/211 applicable to the inspection involved and Bioavailability (21 CFR 320). In the case of APIs, review FD&C Act section 501(a)(2)(B) [21 U.S.C 351(a)(2)(b)] and the ICH industry guideline entitled "Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients."
Review the current editions of the United States Pharmacopeia (USP), and Remington's Pharmaceutical Sciences for information on specific products or dosage forms. For compounding pharmacies, review USP Chapters 795 and 797. IOM 1.10.3 also provides a link to a consolidated list of pertinent guides and guidelines which may be applicable during drug inspections.
Review 21 CFR 203 "Prescription Drug Marketing", 21 CFR 205 "Guidelines for State Licensing of Rx Drug Distributors", and CP 7356.022, Enforcement of the Prescription Drug Marketing Act (PDMA).
Before conducting drug preapproval inspections (CP 7346.832) it is important to be familiar with the application and coordinate accomplishment of Center goals communicated by (1) inspectional memos, (2) pre-inspection briefings, and/or (3) Center participation on the inspection team.
Before conducting an inspection that may involve postmarketing adverse drug experience reporting, you should review 21 CFR Sections 310.305, 314.80, 314.98, 314.540, and 600.80, Section 760 of the FD&C Act[21 U.S.C. 379aa], CP 7353.001, and the training video, 'Field Investigators: Adverse Drug Effects (ADE) Detectives,' available online at http://www.fda.gov/Training/ForHealthProfessionals/ucm091001.htm.
The Office of Manufacturing and Product Quality (OMPQ) in CDER has established two mechanisms for you to obtain technical assistance before, during, or after an inspection: 
  1. Office of Manufacturing and Product Quality (OMPQ) Subject Contacts.  This list contains the names and phone numbers of OMPQ individuals identified as technical specialists in various areas.
  2. Questions and Answers on Current Good Manufacturing Practices for Drugs (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm124740.htm).  This forum is intended to provide timely answers to questions about the meaning and application ofCGMPs for human, animal, and biological drugs, and to share these widely.  These questions and answers generally clarify statements of existing requirements or policy.

 5.5.1.2 - Inspectional Approach

Follow Compliance Program Guidance Manual (CP) 7356.002 and others as appropriate when conducting CGMP inspections.  In-depth inspection of all manufacturing and control operations is usually not feasible or practical. A risk-based systems audit approach is recommended in which higher risk, therapeutically significant, medically necessary, and difficult to manufacture drugs are covered in greater detail during an inspection. (Note: The status of a drug as medically necessary is determined by CDER, Office of New Drugs, Drug Shortages; They can be reached at 301-796-1300 and via email - drugshortages@fda.hhs.gov) The latter group includes, but is not limited to, time release and low dose products, metered dose aerosols, aseptically processed drugs, and formulations with components that are not freely soluble.
CP 7356.002 incorporates the systems-based approach to conducting an inspection and identifies six (6) systems in a drug establishment for inspection: Quality, Facilities and Equipment, Materials, Production, Packaging and Labeling and Laboratory Control Systems.  The full inspection option includes coverage of at least four (4) of the systems; the abbreviated inspection option covers of at least two (2) systems. In both cases,  CP 7356.002, indicates the Quality System be selected as one of the systems being covered.  During the evaluation of the Quality System it is important to determine if top management makes science-based decisions and acts promptly to identify, investigate, correct, and prevent manufacturing problems likely to, or have led to, product quality problems.
When inspecting drug manufacturers marketing a number of drugs meeting the risk criteria, the following may help you identify suspect products:
  1. Reviewing the firm's complaint files early in the inspection to determine relative numbers of complaints per product.
  2. Inspecting the quarantine, returned, reprocessed, and/or rejected product storage areas to identify rejected product.
  3. Identifying those products which have process control problems and batch rejections via review of processing trends and examining reviews performed under 21 CFR 211.180(e).
  4. Reviewing summaries of laboratory data (e.g., laboratory workbooks), OOS investigations, and laboratory deviation reports.

 5.5.1.3 - CDER Bio-research Monitoring

Bio-research monitoring (BIMO) assignments for drugs will generally be issued by the Center for Drug Evaluation and Research (CDER) (see IOM 5.5.6).

 5.5.2 - DRUG REGISTRATION & LISTING

Registration and listing is required whether or not interstate commerce is involved. See Exhibit 5-12 and IOM 2.9.1.1 for additional information.
Two or more companies occupying the same premises and having interlocking management are considered one establishment and usually will be assigned a single registration number. See IOM 5.1.1.11 - Multiple Occupancy Inspections for additional information.
Independent laboratories providing analytical or other laboratory control services on commercially marketed drugs must register.
FACTS will indicate if the establishment is registered for the current year. If you determine registration and listing is required, advise your supervisor. After checking for past registration, cancellation, etc., the district will provide the firm with the proper forms and instructions.
Each establishment is required to list with FDA every drug in commercial distribution, whether or not the output of such establishment or any particular drug so listed enters interstate commerce.  During the establishment inspection, you should remind the firm of its responsibilities for ensuring its drug listing accurately reflects the current product line and updating its listing as necessary to include all product changes, NDC changes, and discontinuations in accordance with 21 CFR 207. If registration and listing deficiencies are found, document it in your EIR, collect a documentary sample and/or contact your supervisor.

 5.5.3 - PROMOTION AND ADVERTISING

21 CFR 202.1 which pertains only to prescription drugs, covers advertisements in published journals, magazines, other periodicals, and newspapers, and advertisements broadcast through media such as radio, television, and telephone communication systems. Determine what department or individual is responsible for promotion and advertising and how this responsibility is demonstrated. Ascertain what media (radio, television, newspapers, trade journals, etc.) are utilized to promote products.
Do not routinely collect examples of current advertising. Advertising should be collected only on assignment, or if, in your opinion, it is clearly in violation of Section 502(n) of the FD&C Act [21 U.S.C. 352 (n)] or 21 CFR 202.1.