Quality Training – Indianapolis Section ASQ Monthly Meetings

Did you know…That the Indianapolis Section (Section 903) of the American Society for Quality meets on the second Tuesday of each month September through May at the University of Indianapolis?  However, if you are not able to attend the meeting you still have the ability to view the information as the presentations are videotaped and uploaded to the internet at the Indy ASQ website.

The videos are located here. (note you may need to refresh)

Additional information concerning the Indianapolis Section of ASQ may be found here.

Track and Trace Legislation

How many commercials have you watched where the purchaser of a used car is advised to ask for the car fax, in order to learn about the history of the car prior to purchasing it? If we can track the history of an automobile, surely we should be able to track the history of the nation’s drug supply.

On September 25, 2013, as identified in an Energy Commerce Committee press release, leaders from the Senate and House committees overseeing health policy announced that they have reached an agreement on legislation to help ensure the safety of compounded drugs and our nation’s pharmaceutical supply chain.  This legislation, the Drug Quality and Security Act, HR 3204, reflects a bipartisan, bicameral effort to improve drug safety and help prevent a future public health crisis like the 2012 meningitis outbreak tied to the New England Compounding Center.

HR 3204, would replace today’s patchwork of state prescription-drug tracing laws by creating a new uniform framework for tracking drugs from the manufacturer to the pharmacy.  There is currently no system for tracking the drugs that make up some four billion prescriptions per year in the United States, which means drugs that are stolen or counterfeit may not be discovered before reaching consumers.

This will provide the FDA the ability to track and trace drugs through the supply chain from point of manufacture to the distribution point.  This should allow for tracking of drugs up to 10-years from the date of manufacturing.

http://energycommerce.house.gov/press-release/senate-house-health-policy-leaders-announce-bipartisan-bicameral-legislation-address

Shamrock Medical Solutions Group

In a September 18, 2013 press release by USFDA, federal judge Algenon L. Marbley of the Southern District of Ohio has approved a consent decree of permanent injunction against Shamrock Medical Solutions Group, LLC, of Lewis Center, Ohio, and four of its corporate officers and employees for continued drug manufacturing and labeling violations that resulted in the distribution of mislabeled drugs.

A June 2012 warning letter identified repackaging technicians had changed master labels of repackaged products, which resulted in product packages labeled with incorrect strength or incorrect spelling of the drug name. An April 2010 warning letter identified a lack of validation for the practice of splitting and repackaging tablets, and a lack of cleaning validation.

To resume operations according to the consent degree – the company must first notify the FDA of their intentions. The firm will not be able to resume operations until they receive written notice from the FDA that their operations are compliant with the Federal Food, Drug, and Cosmetic Act and all applicable regulations. Prior to resuming operations, the consent decree also requires Shamrock Medical to retain an independent expert to inspect their operations and have the expert certify to the FDA that the necessary corrections have been made. The consent decree also requires Shamrock Medical, upon resumption of its operations, to comply with CGMP regulations.

 

Unique Device Identification Rule (UDI)

The final rule for implementation of a unique device identifier or UDI has been released and will be posted on the following FDA page on 9-24-13.  Additionally, the FDA has posted the Global Unique Device Identification Database (GUDID) draft guidance available here.

The FDA has provided a summary of compliance dates for the UDI final rule.

1 year after publication – The labels and packages of class III medical devices and devices licensed under the Public Health Service Act (PHS Act) must bear a UDI. § 801.20.
Dates on the labels of these devices must be formatted as required by § 801.18. Data for these devices must be submitted to the GUDID database. § 830.300.

2 years after publication – The labels and packages of implantable, life-supporting, and life-sustaining devices must bear a UDI. § 801.20. Dates on the labels of these devices must be formatted as required by § 801.18.  A device that is a life-supporting or life-sustaining device that is required to be labeled with a UDI must a bear UDI as a permanent marking on the device itself if the device is intended to be used more than once and intended to be reprocessed before each use. § 801.45.
Stand-alone software that is a life-supporting or life-sustaining device must provide its UDI as required by § 801.50(b). Data for implantable, life-supporting, and life-sustaining devices that are required to be labeled with a UDI must be submitted to the GUDID database. § 830.300.

3 years after publication – Class III devices required to be labeled with a UDI must bear a UDI as a permanent marking on the device itself if the device is a device intended to be used more than once and intended to be reprocessed before each use. § 801.45.  The labels and packages of class II medical devices must bear a UDI. § 801.20. Dates on the labels of these devices must be formatted as required by § 801.18.  Class II stand-alone software must provide its UDI as required by § 801.50(b).Data for class II devices that are required to be labeled with a UDI must be submitted to the GUDID database. § 830.300.

5 years after publication – A class II device that is required to be labeled with a UDI must bear a UDI as a permanent marking on the device itself if the device is a device intended to be used more than once and intended to be reprocessed before each use. § 801.45.  The labels and packages of class I medical devices and devices that have not been classified into class I, class II, or class III must bear a UDI. § 801.20. Dates on the labels of all devices, including devices that have been excepted from UDI labeling requirements, must be formatted as required by § 801.18.  Data for class I devices and devices that have not been classified into class I, class II, or class III that are required to be labeled with a UDI must be submitted to the GUDID database. § 830.300.  Class I stand-alone software must provide its UDI as required by § 801.50(b).

7 years after publication – Class I devices, and devices that have not been classified into class I, class II, or class III that are required to be labeled with a UDI, must a bear UDI as a permanent marking on the device itself if the device is a device intended to be used more than once and intended to be reprocessed before each use. § 801.45.

Compounding Pharmacies Legislative Action

The US Congress is taking action to put compounding pharmacies under greater control of the USFDA.  The US Senate introduced S. 959 Pharmaceutical Quality, Security, and Accountability Act May 15, 2013, and the House has introduced H.R. 3089 To amend section 503A of the Federal Food, Drug, and Cosmetic Act with respect to pharmacy compounding September 12, 2013,

According to Ethridge (2013), both bills create a new pharmacy category, for pharmacies that compound sterile produces and ship across state lines, these facilities would be regulated by FDA.

While both of these bills are in the early stages and subject to change during the legislative process, according to Ethridge (2013) the current versions would require the compounding facilities register with FDA, submit a compounding list, adverse event reporting, product labeling, and would be subject to FDA inspection.

Process and production errors associated with sterile compounding first became known from the Meningitis outbreak linked to the New England Compounding Center.  As of March 13, 2013 there have been 50 fatalities, with another 722 people still sick with infections (Sweet, 2013).

Ethridge, E. (2013).  House Bill would Expand FDA Role in Pharmacy Oversight. CQ News. Retrieved from http://tinyurl.com/mfoq3vv

Sweet, L. (2013) Deaths continue in Meningitis outbreak tied to Framingham pharmacy. Boston Herald.  Retrieved from http://tinyurl.com/lw9xhva

Current Inspection Trends From FDA Warning Letters

A review of warning letters posted on September 10, 2013, to the FDA website was conducted.  Four of thirteen warning letters were issued by CDRH with a subject of Quality System Regulation for Medical Devices/Adulterated.  Twenty-seven violations were identified at these four manufacturers.  A break-down of the identified violations follows:

Citation                                      Subpart (Frequency)

21 CFR 820.30 (b,d,f,g,i)           Design Controls (7)
21 CFR 820.100                        CAPA (4)
21 CFR 820.50 (a,b)                 Purchasing Controls (3)
21 CFR 820.75(a)                     Process Validation (3)
21 CFR 820.70(a,c)                  Production & Process Controls (2)
21 CFR 820.198                       Complaint Files (2)
21 CFR 820.22                         Quality Audit (1)
21 CFR 820.40                         Document Controls (1)
21 CFR 820.86                         Acceptance Status (1)
21 CFR 820.90                         Nonconforming Product (1)
21 CFR 820.120                       Device Labeling (1)
21 CFR 820.250                       Statistical Techniques (1)                1

It is interesting to note that:

Warning Letter Bio Focus addresses issues with IQ, OQ and PQ.  Specifically where acceptance criteria was not specified and the OQ as required by the firms validation procedure was not performed.

Warning Letter Vision RT addresses a number of issues concerning Design Controls.  Specifically where design changes were not implemented in accordance with firm procedures, the firm did not assure testing of production units were conducted under actual or simulated use, and lack of a statistical justification for sampling size.  Additionally, design verification was not conducted, the essential design outputs were not identified, and no planning document was available for the project.

FDA Delays Conformance Date to IEC 60101 v3

FDA Extends Deadline for Conformity to IEC 60601-1 3rd Edition medical device electrical standard compliance to December 31, 2013.  The original date to demonstrate conformance was July 30, 2013.  This standard contains requirements concerning basic safety and essential performance that are generally applicable to medical electrical equipment.  After Dec 31, 2013, all submissions to the U.S. FDA for device approval must conform to version 3 of the standard.
Intertek has provided a guide that describes the changes from version 2, and includes a clause by clause review of the new standard.

Compounding Pharmacies in the News…

Compounding pharmacies remain in the news. Most recently the Stewart Compounding Pharmacy in Fayetteville, NC received a warning letter (posted on the FDA Warning letter Website on 8-21-13), based on an FDA inspection March 18 to 25, 2013. The violations identified in the warning letter included:

  1. Failure to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes [21 CFR 211.113(b)].
  2. Failure to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination [21 CFR 211.28(a)].
  3. Failure to establish an adequate system for monitoring environmental conditions in aseptic processing areas [21 CFR 211.42(c)(10)(iv)].
  4. Lack of for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product [21 CFR 211.167(a)].
  5. Failure to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)].
  6. Lack of, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release [21 CFR 211.165(a)].

3-D Printing

As personal medicine develops and medical devices move from mass to customized production this poses obvious questions on how these devices will be regulated. Imagine a future where a patient performs a CT scan in the morning, a custom implant is built (3-D printed) in the afternoon, and surgery in the evening…

More from Steven Pollack, Director of FDA’s Office of Science and Engineering Laboratories (OSEL) (FDA Blog):

http://blogs.fda.gov/fdavoice/index.php/2013/08/fda-goes-3-d/

Performance Validation Launches New Website

Performance Validation, LLC is pleased to launch our newly revised website.  The site has been completely re-written in WordPress, is mobile device friendly, faster loading, and includes new content, such as a leadership page, blog, etc., that should provide a better user experience.  Stay tuned, as we will be adding new content, e.g., project summaries, and white papers in the near future.  Enjoy,

Rick Van Doel, President, Performance Validation