Best practice paper on visual inspection to be published in September 2014


The ECA working group on visual inspection, which was founded this year, is going to publish its first document during the ECA event Particles in Parenterals and beyond. Read more.,Z-PEM_n.html

Press Announcement: Best practice paper on visual inspection to be published in September 2014

The work on this best practice paper has already started earlier this year and has been intensified since the foundation of the working group in March 2014. The goal of this paper is to harmonise the long lasting experience and knowledge from different and approved industrial practices and from presentations from previous conferences.
The paper, which is much rather supposed to be a reference than a strict requirement, will cover Manual and Automated Inspection issues in the following chapters:

  • Workplace (manual)
  • Operation (manual and automated)
  • Qualification
  • Re-Qualification
  • Re-Validation
  • Evaluation of defects
  • Batch release considerations

The paper is still in the group internal discussion phase, but it will be published in its first version during the ECA conference “Particles in Parenterals and beyond” scheduled in Copenhagen, Denmark, from 24-25 September 2014. All participants of the event will receive a copy of this document.

In the future course of this year, the group will decide whether it will be transferred to an interest group which would then allow to further discuss and supplement the content of the paper and to possibly admit further group members.
More information will be published on the group’s webpage, when available.

Handling of OOS Results in Europe


FDA’s Guidance on Out-of-Specification Results has been seen as the state of the art regarding the handling of OOS results. In the meantime, Europe – through the British MHRA and the German ZLG – has also developed requirements on that topic. Read more here about the most important regulations of the respective guidance documents.


GMP News: Handling of OOS Results in Europe,8430,Z-QCM_n.html

For some time now, information about the handling of OOS results has been put on the website of the MHRA. There, you can find a Guidance document entitled “Out of Specification Investigations”. This document was updated last year to add microbiological aspects.

It is easier to understand than the FDA Guideline on the same topic. The different Flow Charts are also helpful.

A definition of all terms – both Out-of-Specification (OOS) Results and Out of Trend (OOT) Results – is provided at the beginning as well as atypical / aberrant / anomalous results. A definition of the term “Reportable Result” is also provided as follows: “is the final analytical result. This result is appropriately defined in the written approved test method and derived from one full execution of that method, starting from the original sample.”

Regarding averaging, it is explicitly said that it “must be specified by the test method”. Moreover, the 95% Confidence Limit must be taken into consideration when averaging is used.

Retesting may be performed if no assignable cause can be found to explain a deviating result. Retesting should be performed on the original sample not on a different sample. Regarding the number of retests required, the MHRA refers to other publications suggesting 5, 7 or 9 retests. Retest results shouldn’t be averaged with the original results which triggered the OOS investigation.

Like in the FDA Guidance, an outlier test solely can’t be considered as sufficient to justify the rejection of data.

Also the aspect of OOS and OOT results for stability testing is addressed.

For quite a long time, Germany has been using the ZLG Aide Mémoire (Zentralstelle der Länder für Gesundheitsschutz bei Arzneimitteln und Medizinprodukten) on the monitoring of manufacturers of medicinal products; section 6.8 also addresses the handling of OOS results. With regard to retesting, the Aide Mémoire defines that the number of retests should be set in advance in an SOP based on sound scientific judgement and should be statistically valid.

The ZLG Aide Mémoire also states that averaging is allowed: the average value must correspond to the specification, but single results must not. However, it is a condition that acceptance criteria should be defined for the variability of the single values and that these provisions are described in an SOP.

You can find more information in the MHRA Guidance Document Out-of-Specification Investigations here as well as in the ZLG Aide Mémoire on the monitoring of manufacturers of medicinal products.

FDA warns consumers: Dietary supplements cannot treat concussions

Atasteofcreole's Blog

The U.S. Food and Drug Administration is warning consumers about dietary supplements that falsely claim to prevent or cure concussions or other traumatic brain injuries. The FDA says supplements with labels that make these claims are not backed up by scientific evidence, and in a consumer alert issued Monday it urged users to beware.

Additionally, the FDA says some companies have marketed these products to military service members and veterans who have sustained combat-related traumatic brain injuries. The U.S. Department of Defense was among the first to raise concerns.

The warning comes as school is starting up again many student athletes are getting back into competitive sports that can lead to concussion and other serious injuries. The risk for head trauma from contact sports, such as football and wrestling, has provided another marketing opportunity for companies to make false claims that certain dietary supplements can help cure or prevent…

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Indian Sterile Manufacturer receives FDA Warning Letter and changes company name from Marck Biosience to Amanta Healthcare

Marck Biosciences Ltd. to “Amanta Healthcare Ltd.”, effective from June 24, 2014.

Click here to visit  website at


Indian Sterile Manufacturer receives FDA Warning Letter and changes company name from Marck Biosience to Amanta Healthcare

Marck Biosciences Limited is a producer of sterile products which has been producing sterile products for the US market. The FDA Warning Letter dated July 8, 2014 contains shocking details about the GMP situation at this facility. Read more here about the FDA Warning Letter to Marck Biosciences and about the name change to Amanta Healthcare.


Which SOPs are required by GMP?

ECA is receiving a lot of questions on SOPs (Standard Operating Procedures) needed in a GMP environment. The most interesting is the one on which SOPs are required by law. Here is an Overview.

GMP News: Which SOPs are required by GMP?

The ECA Academy is receiving a lot of questions on SOPs (Standard Operating Procedures) needed in a GMP environment. The most interesting is the one on which SOPs are required by law. Here is an Overview:

U.S. Food and Drug Administration (FDA):

A three year old Notice focusing on specific recordkeeping requirements in the Federal Register also gives a very good summary of SOPs required by 21 CFR Part 211:

“Written procedures (standard operating procedures – SOPs), are required for many Part 211 records. The current SOP requirements were initially provided in a final rule published in the Federal Register of September 29, 1978 (43 FR 45014), and are now an integral and familiar part of the drug manufacturing process.”

The 25 SOPs provisions under Part 211 include:

  • Section 211.22(d)-Responsibilities and procedures of the quality control unit;
  • Section 211.56(b)-Sanitation procedures
  • Section 211.56(c)-Use of suitable rodenticides, insecticides, fungicides, sanitizing agents;
  • Section 211.67(b)-Cleaning and maintenance of equipment;
  • Section 211.68(a)-Proper performance of automatic, mechanical, and electronic equipment;
  • Section 211.80(a)-Receipt, identification, storage, handling, sampling, testing, and approval or rejection of components and drug product containers or closures;
  • Section 211.94(d)-Standards or specifications, methods of testing, and methods of cleaning, sterilizing, and processing to remove pyrogenic properties for drug product containers and closures;
  • Section 211.100(a)-Production and process control;
  • Section 211.110(a)-Sampling and testing of in-process materials and drug products;
  • Section 211.113(a)-Prevention of objectionable microorganisms in drug products not required to be sterile;
  • Section 211.113(b)-Prevention of microbiological contamination of drug products purporting to be sterile, including validation of any sterilization process;
  • Section 211.115(a)-System for reprocessing batches that do not conform to standards or specifications, to insure that reprocessed batches conform with all established standards, specifications, and characteristics;
  • Section 211.122(a)-Receipt, identification, storage, handling, sampling, examination and/or testing of labeling and packaging materials;
  • Section 211.125(f)-Control procedures for the issuance of labeling;
  • Section 211.130-Packaging and label operations, prevention of mixup and cross contamination, identification and handling of filed drug product containers that are set aside and held in unlabeled condition, and identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch;
  • Section 211.142-Warehousing;
  • Section 211.150-Distribution of drug products;
  • Section 211.160-Laboratory controls;
  • Section 211.165(c)-Testing and release for distribution;
  • Section 211.166(a)-Stability testing;
  • Section 211.167-Special testing requirements;
  • Section 211.180(f)-Notification of responsible officials of investigations, recalls, reports of inspectional observations, and any regulatory actions relating to good manufacturing practice;
  • Section 211.198(a)-Written and oral complaint procedures, including quality involving specifications failures, and serious and unexpected adverse drug experiences;
  • Section 211.204-Holding, testing, and reprocessing of returned drug products; and
  • Section 211.208-Drug product salvaging.

European Union:

SOPs required by EU-GMP are mainly defined in the EU Guidelines to Good Manufacturing Practice of Eudralex Vol. 4 (EU-GMP Guide). There is no comprehensive list provided but Chapter 4 of Part 1 (Documentation) of the Guide gives some examples:

“There should be written policies, procedures, protocols, reports and the associated records of actions taken or conclusions reached, where appropriate, for the following examples:

  • Validation and qualification of processes, equipment and systems;
  • Equipment assembly and calibration;
  • Technology transfer;
  • Maintenance, cleaning and sanitation;
  • Personnel matters including signature lists, training in GMP and technical matters, clothing and hygiene and verification of the effectiveness of training.
  • Environmental monitoring;
  • Pest control;
  • Complaints;
  • Recalls;
  • Returns;
  • Change control;
  • Investigations into deviations and non-conformances;
  • Internal quality/GMP compliance audits;
  • Summaries of records where appropriate (e.g. product quality review);
  • Supplier audits.”

Chapter 4.30 requires that operating procedures “should be available for major items of manufacturing and test equipment.”

World Health Organisation (WHO)

A very comprehensive list can be found in the WHO guide to good manufacturing practice (GMP) requirements, Part 1: Standard operating procedures and master formulae. Although written as part of the Global Programme for Vaccines and Immunization, Vaccine Supply and Quality, this overview gives valuable guidance also for other pharmaceutical companies.

More than 75 SOPs are listed from the following areas in Appendix 1 (“List of Document Requirements”):

  • Raw Materials
  • Biological Starting Materials
  • Facility
  • Equipment (Production and QC)
  • Production
  • Labelling and Packaging
  • Quality Control
  • Quality Assurance

The examples from FDA, EU and WHO provided above are not a finite list. Some topics might be split in a number of SOPs for the sake of practicality. Some other company or quality system specific processes might be defined in SOPs as well.

Wednesday, 20 August 2014 Glenmark enters Oncology with the Discovery and the Initiation of IND enabling Studies of an innovative bispecific Antibody

New Drug Approvals

August20, 2014: Glenmark Pharmaceuticals S.A. (GPSA), a wholly owned subsidiary of Glenmark Pharmaceuticals Limited India (GPL), announces the discovery and initiation of IND enabling studies of a novel clinical development candidate, GBR 1302, a HER2xCD3 bispecific antibody. GBR 1302 was discovered and developed by the Glenmark Biologics Research Centre located in La Chaux-de-Fonds, Switzerland. GBR 1302 is based on Glenmark’s innovative BEAT antibody technology platform which facilitates the efficient development and manufacture of antibodies with dual specificities, so-called bispecific antibodies. GBR 1302 is the first clinical development candidate based on the BEAT technology. Glenmark expects to obtain approval for the initiation of clinical studies during this financial year.


·GBR 1302 is the first bispecific antibody based on Glenmark’s proprietary BEAT platform

  • GBR 1302 is Glenmark’s first clinical candidate targeting oncology indications

    Glenmark Pharmaceuticals announced the discovery and initiation of IND enabling studies of a novel clinical development candidate…

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Turkish man pleads guilty to importing illegal cancer drugs


August 15, 2014


Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.

Akman pleaded guilty in the U.S. District Court for the Eastern District of Missouri, in St. Louis, Missouri, where he initially shipped his illegal drugs. The drugs did not meet the FDA’s standards and had not been approved for distribution in the United States.

The FDA’s Office of Criminal Investigations coordinated a complex, multi-layered international investigation that led to Akman’s arrest in Puerto Rico in January 2014. The investigation identified Akman and his company as a source of Altuzan, the Turkish version of the cancer treatment drug Avastin.

“These criminals exploited our most vulnerable patients when they arranged for their illicit drugs to be brought into the United States and used to treat cancer patients. We will continue to investigate and bring to justice those who prey on our ill, susceptible patients,” said Philip J. Walsky, acting director of the FDA’s Office of Criminal Investigations. “We commend our colleagues – international, national, state, and local – whose contributions helped bring this case to a successful conclusion.”

Akman, along with his employee, Ozkan Semizoglu, obtained the illicit drugs and then used shipping labels to conceal the illegal nature of the shipments, including customs declarations falsely describing the contents as gifts. They also broke large drug shipments into several smaller packages to reduce the likelihood of seizures by U.S. Customs and Border Protection authorities.

Along with the FDA and Europol, the international operation involved several German government offices: the Bonn prosecutor; the Federal Criminal Police, the Dusseldorf police, and the German State Criminal Police.  Special agents of the U.S. Department of State’s Diplomatic Security Service assigned to the U.S. Embassy’s Regional Security Office in Ankara, Turkey, and the U.S. Consulate General’s Overseas Criminal Investigations Branch in Istanbul, Turkey also played key roles in the successful resolution of this case.