Tuesday, September 10, 2013

SMEs likely to play important role in pharma growth story: report

SMEs likely to play important role in pharma growth story: report

Sunday, December 2, 2012

Experience Quality, not measure it.

Going thru an interesting title 'Quality is personal' reminds me of my 2 years earlier post 'Quality is free'. Indeed the book I am reading is a best seller of its own kind, and my post was influenced by a comment made by one of my earlier boss in a conference.

If Quality is personal, it is definitely free.

Requires, just an attitude towards perfection, beauty, contentment or satisfaction, quality is indeed a sense of fulfillment.

However, within a world of consumerism, industrialization and the way concept of quality emerged and taken place in text books of management, its seen with a myopic view of improvement in processes, systems and calibration of machines or services.

There is, nevertheless, another key lesson, which is the basis of beliefs. Quality as practices by the individual is the foundation on which total quality management is built. I recall an anecdote where in a sales executive who charge another couple of dollars for explaining how a digital watch works to her customer. On the other hand, when the same customer happen to visit another country, he was given a free gift wrapping of a cheap gift item he purchased from the store. Delighted, the left the store with a smile and pledging to come back again if he happens to visit again that country.

Quality can not be taught, it can only be experienced, learned and re-learned. There is however, no point of unlearning in quality. Experience Quality and do not measure it.

Steve Jobs during his various sessions in developing his elite gadgets, didn't like the models, crafting or whatsoever was brought in front of him. Simple, there was no reason, but he didn't like them. He was actually building quality into his products from his own eyes.

So, is quality an idea? a thought? an endeavor for evolution of mankind towards a better society?

Saturday, October 20, 2012

Deviations & CAPA remains hot topic in Audits

MHRA Publishes set of information from its database summarizing their observations to show deviations and CAPA remains the hot topic for inspectors during their regular GMP inspections.

While investigations of anomalies (deviations, OOS, OOTs) remains at the top, insufficient CAPA comes at third position.

MHRA has come forward to publish some of the reasons for this continuous concern over the years. These questions and relevant answers give a good overview and tips on how EU inspectors review QRM elements from ICH Q9 and Q10 and how do they enforce them.

The details presentation can be downloaded at, click here

The tips and frequently asked questions regarding inspectors approach towards QRM can be downloaded, click here

Thursday, May 24, 2012

MHRA Publishes OOS FAQs

FDAs guidance on Out-of-specifications (OOS) is well known. Now Guidance from the MHRA on how to handle out-of-specification results during laboratory analysis is - on the contrary - pretty unknown although an own webpage on the MHRA website is dedicated to the OOS topic.

On the MHRA website, you can find a complete presentation on Out Of Specification Investigations. The presentation ends with the following statement: "Microbiological expectations will be provided at a later date."

These FAQs and interactive presentation provide guidance on what to do if an out of specification result is identified during laboratory analysis.

Click here to read and download the guidance.

Friday, January 27, 2012

Warning Letter, AIP to Consent Decree - Isn't it then better to follow GMPs ?

In continuation to my earlier post related to AIP featuring Ranbaxy's and FDA saga, the 'consent decree' might be the forward looking statement to both the parties. While FDA moves ahead with caution and pre-fixed direction, Ranbaxy makes firm committment towards its Quality Assurance program and prmomise to provide safe and quality medicines.

Consent decree is an order issued by a judge that expresses a voluntary agreement by the participants in a lawsuit. Sometimes a suit ends when a judge issues a consent decree, or a consent judgment. This is especially the case when the decree is issued after one side of the case voluntarily agrees to cease a particular action without admitting to any illegality of the action.

If a firm has repeatedly violated cGMP requirements, the FDA may make a legal agreement with the firm to force them to make specific changes; the agreement, the consent decree, is enforced by the federal courts. Usually, consent decrees include fines ("disgorgements"), reimbursements to the government for inspection costs, due dates for specific actions, and penalties for noncompliance. Consent decrees usually are permanent, but at times specified in the agreement when the firm has achieved compliance, it can petition the court to remove the decree.

Historically many companies have been a part of consent decree and notably are Schering & Plough, J& J.

More information can be obtained at click here

Monday, October 31, 2011

Excipients to get Certification standards

The Excipients finally have come inside the auditing ring.
The much awaited standards for auditing Excipients is going to release. The standards, known as Excipact some time in January 2012. IPEC, the excipients association says that this standard will give suppliers, users and auditors manufacturing and distribution standards that ensure product quality and minimize regulatory burden.

The safety of medicines for patients is paramount to all those involved in the supply chain. To assure the quality of medicines produced, risks in the supply chain need to be evaluated and minimized, and this includes not only active pharmaceutical ingredients (APIs) but also pharmaceutical Excipients.
At the same time, the major Excipients manufacturers are working hard to keep pace with the growing formulations, various delivery systems and technologies. Therefore, various important features are being considered in their Excipients product portfolio to influences Excipients role during formulations development. For example, BASF says role of solubility and bio availability will be key focus for its pharmaceutical excipient product development efforts for next few years.
Also the price rise among Excipients and cut throat competition compels their manufacturers to invent niche processes in shortest period of time, however maintaining the best quality for formulation development.
Going by the technologies and studies put into the Excipients development process, it was paramount that the regulatory agencies must have framed up GxP model for assessing quality for manufacturing these goods.
To download these standards, click here

Thursday, September 8, 2011

Tablets Scoring. FDA release its guidance to industry

It was just last month while dispensing a tablet for my wife, which was on a higher dosage, I need to adjust the dosage but realized it was rather difficult to break or split it in two pieces to get it of lower dosage as prescribed by the physician. The difficulty in breaking it was due to the fact, the tablet was not scored.
As it was also film coated, the split or broken piece was to be therefore exposed before consumption in next dosage. The dilemma remained and I tried to take precautionary measures. I knew it and so I did it, but what for those who are unaware of handling split fractions of tablets?
But my dilemma was over last week, when Ashish forwarded the new guidance for industry from FDA. This new guidance is on Tablets Scoring: its nomenclature, labeling and data for evaluation.
A good initiative as usual from the FDA. While the guidance will help people like me who may have to dispense broken tablets. The issues are related to dealing with modified released tablets, stability of split tablet, risks of impurity generation etc.
These are set of guidance’s and criteria for industry on which scored tablets characteristics will be evaluated as part of review process.
The guidance can be downloaded from the FDA site or click here.

Tuesday, August 30, 2011

EU GMP Guide: New Requirements added for Batch Certification

In Part III of the EU GMP Guide, a document on internationally harmonised requirements for batch certification has been added. It is applicable in the context of Mutual Recognition Agreements (MRA), Agreements on Conformity Assessment and Acceptance of Industrial Products (ACAA) and other appropriate arrangements on GMP with the European Union.
Each batch of medicinal product transferred between countries having appropriate arrangements on GMP, must be accompanied by a batch certificate issued by the manufacturer in the exporting country. In the framework of MRAs all manufacturing sites must be located in the country issuing the certificate or in another MRA country, if reciprocal arrangements are in force. In the framework of the European Union's ACAA with Israel (once in operation) all quality control sites must be located in Israel or the EU.
The respective certificate should be issued further to a full qualitative and quantitative analysis of all active and other relevant constituents to ensure that the quality of the products complies with the requirements of the marketing authorisation of the importing country. It shall attest that the batch meets the specifications and has been manufactured in accordance with the marketing authorisation of the importing country. The batch certificate should be signed by the person responsible for certifying that the batch is suitable for release for sale or supply/export. For the EU, that's the Qualified Person (QP).
Where applicable this batch certificate shall also be used for non-finished medicinal products such as intermediates, bulk or partially packed products.
The certificate may also be used for active pharmaceutical ingredients (API) and investigational medicinal products (IMP) used in clinical trial authorisations.

Click here to download the full document

Thoughts, ideas and quality.

Its been a long time in my endeavour to blogging or more precisely writing my thoughts. Not because, I was too occupied, or lack ideas, but somehow I was lagging the enthusiasm for writing. Anyhow, better later than never and so I am back again.

In one of my earlier post, I mentioned about quality as an idea. This is just an extension of my earlier though emphasising on thought and idea and their correlation with quality.

Ideas emerge from thoughts and thoughts are numerous, continuous, useful or may be gibberish at times, but thoughts provide a good soil for ideas to grow. A thoughtful mind is full of ideas which are are instantaneous, triggered by passion for resolving issue or to find ways of moving forward.

Quality is perception towards object or happening. An idea is an impetus to this perception. Ideas emerge when there are thoughts. 

Quality of thoughts, design ideas and will generate same quality of ideas.

Wednesday, June 1, 2011

Audits - Boon or bane?

Are continuous audits really helpful in improvement? Does audits really increase the band width of quality systems or it has taken the shape of mere formality? and the things continue the way they are?

The importance to the business in identifying risks within a department’s operating procedures has become more and more pronounced but many auditors complain that they operate with one hand behind their back as department heads will often ignore, reject or delay the implementation of the recommendations being presented.

What do you say ? as an Auditor or as an Auditee ? The rudimentary question is continuous improvement, compliance to laid down regulations versus fast deliveries at the cost of ?

Sunday, January 9, 2011

Is Quality an Idea ?

From an old post in Plaxo;

Ideas never die. Ideas live forever. Once the germ of an idea is born..it remains. So is quality also an idea ? Is quality a thought ? or attitude ? or pursuit for excellence ? whatever it is, but why it is what it is. The philosophical debate on quality will continue. It will give many answers which may or may not fit best to the question that what quality is!

I remember entering the room of a Manager of one pharma company which was tidy, neat and well maintained. The placement of pens and pencils in the pen holder, colours, sketch pens, books, charts and chair - in fact everything was wonderful. Or did I only think that was wonderful ? My attitude or his attitude ?

Alfred Nobel, so distress from his invention of dynamite, raised his wealth for an award - Nobel prize. He thought rather unusual - a quality thought? Does thoughts also have quality ?

But had he never had so much of wealth to offer, what Alfred would have done?? No money - no award. The quality of Life...

You never know - quality is multidimensional, multifaceted, omnipresent and mysteriously hidden in the seed of human thoughts - human thought which have the courage to raise this civilization! Is it?

Is quality an Idea ?

Wednesday, September 29, 2010

Template for API Quality Agreement

BPTF or Bulk Pharmaceutical Task Force, a SOCMA organization has launched a template for preparing quality agreement to provide guidance for drafting agreements related to the manufacture and release of drug substances regulated by various regulatory agencies. The template is based on the experience of industry members.

For more information and downloading of the template, click here

Thursday, September 16, 2010

Schedule L1, GLP on board !

Thanks to Mr Shirgaonkar for this wonderful information !
Knowledge of Good Laboratory Practices is very important in Pharmaceutical industry.
New GLP requirements as per Schedule L1 of Drug Rules will come into effect from 1st November 2010. Topics such as General laboratory requirements,instruments calibration, microbiological testing and internal audit will be covered in this statutory requirement.
It was announced that Ministry of Health has recently notified the Schedule L-1 of Rule 74,78 and 150 E under Drugs and Cosmetics Third Amendment Rule 2008 giving the pharmaceutical industry time till November 1, 2010 for compliance.
The implementation of GLP and the responsibility of companies to comply with them while carrying out quality analysis. GLP stresses on the maintenance of documented quality systems as per the quality manual laid down by the manufacturing unit, and on the technical audit of the quality control laboratory for GLP compliance by an expert/experts appointed by the top management other than the person in charge of the laboratory.
As Mr. Shirgaonkar organises a workshop on GLPs and highlight the incumbent Schedule L1, to know more visit Insight Systems website

Friday, September 3, 2010

Revision of Isopropylbenzene status from Class 3 to Class 2

Keyoor has forwarded an interesting information. The jumping of chemicals from one list to another will continue. The information says that ICH is revising the status of Isopropylbenzene to Class 2 from existing Class 3 ! This is somewhat a demotion of Isopropylbenzene which was previously in the safer Class 3. It also means that there will be an upper specification limit to Isopropylbenzene and which must be continuously monitord and controlled.

Although I could not verify the source of this information, but I am sure Keyoor's information is correct and precise. Please read the following text which is copy-paste version:

Due to new toxicity studies in rats and mice, the solvent Isopropylbenzene is meant to be categorised as Class 2 instead of Class 3. A corresponding ICH draft guideline has been published and released for commenting by the public.
The ICH Guideline Q3C defining the limits for residual solvents as impurities in active pharmaceutical ingredients (APIs) and finished medicinal products as well as the methods for establishing their exposure limits has already been revised four times. The revisions concern among others provisions for calculating the PDEs (PDE = permissible daily exposure, denoting the maximum amount of a solvent that may be taken in with a medicinal product) for the solvents N-Methylpyrrolidone and Tetrahydrofuran. Now the guideline is about to be revised once more, the reason being that new toxicological data have been collected on the solvent Isopropylbenzene (called "Cumene" in the guideline). Hitherto, this substance has been categorised as Class 3, i.e. as a solvent with low toxicity. In general, these solvents have PDE values of 50 mg per day or more. Recent toxicity studies conducted in rats and mice clearly showed a heightened carcinogenic potential so that it has become necessary to assign Isopropylbenzene to the higher Class 2 and to calculate the PDE accordingly.
On 26 March 2010, the ICH Draft Consensus Guideline "Impurities: Guideline for Residual Solvents - PDE for Cumene" was published (Step 2 in the ICH process) and has since been available for commenting by the public. This guideline now requires the calculation of the PDE for Isopropylbenzene according to the rules for Class 2 solvents. After two further steps in the ICH process, this guideline will be integrated into the core document, which will then bear the name ICH Q3C(R5).
This new regulation might require manufacturers of APIs and medicinal products using Isopropylbenzene to make a considerable effort in changing their registration dossier (e. g. as a consequence of changes to the manufacturing process, the analytical methods etc.).

Saturday, August 28, 2010

CDSCO Website in its improved version with inclusion of Industry Guidance Documents

CDSCO website in new avatar. Since my last visit to the website, may be at a gap of a year, I realise, CDSCO has included various multidisciplinary topics. Navigation is made easy and search relatively better.
The best part is the inclusion of "Guidance to Industry" documents in the line of US FDA. The recent addition to this is a draft guidance for fixed dose combination.

There are separate sub-section for Medical devices and Diagnostics. Downloads having full text of Drugs & Cosmetics Law;

While all APIs registered as on date in India are listed, there are separate lists for formulations and vaccines registered for import.

There is also a list of all WHO GMP  certified facilities in India which are 817 in number. This information will be useful for foreign manufacturers which wanted to have contract manufacturing or any other kind of in-licensing business from India.

However, still I feel that there could be a better ways of segregation of different categories under the headings of drug products, drug substances, cosmetics, medical devices etc.

Anyway, to start and improve is still better to wait and watch !

To reach the website, click here

Sunday, July 18, 2010

What is AIP ?

AIP is Application Integrity Policy. The policy focuses on the integrity of data and information in applications submitted for Agency (FDA) review and approval.
The AIP described Agency's approach regarding the review of applications that may be affected by wrongful acts that raise significant questions regarding data reliability.
Although the guidance document does not create or confer any rights for or on any person and does not operate to bind FDA or the public, it does represent the Agency's current thinking on consistent implementation of the AIP.
The AIP is invoked when a company’s actions raise significant questions about the integrity of data in drug applications including falsification. Under the AIP, FDA asks the company to cooperate with the agency to resolve the questions of data integrity and reliability. This includes implementing a Corrective Action Operating Plan (CAOP) to provide assurance of the integrity.
To download policy document, click here

Has FDA invoked AIP for any Indian company?
To best of my knowledge, there is no other company from India for which AIP has been invoked, except the Japanese-Indian company - Ranbaxy Laboratories Limited.

Given below is a Case Study on AIP invoked to a company, its consequences and handling of events.
U.S. Food and Drug Administration announced that a facility owned by India-based Ranbaxy Laboratories falsified data and test results in approved and pending drug applications. The facility, Paonta Sahib, was already under an FDA Import Alert since September 2008. To address the falsified data, the FDA has invoked its Application Integrity Policy (AIP) against the Paonta Sahib facility. The AIP is invoked when a company’s actions raise significant questions about the integrity of data in drug applications. Under the AIP, the FDA has asked Ranbaxy to cooperate with the agency to resolve the questions of data integrity and reliability. This would include implementing a Corrective Action Operating Plan (CAOP) to provide assurance of the integrity.

What led FDA to invoke AIP to Ranbaxy?
In the backdrop, when two facilities of Ranbaxy Labs were audited by US FDA Inspectors in the February 2006, the inspections reveal significant deviations from cGMP. Ranbaxy issued three responses (March 20, April 20 and May 25) to these observations. However, the FDAs review of Ranbaxy response didn’t helped much and FDA said in its letter about the still valid concerns.
As these responses and the supporting documentation from Ranbaxy continued to be examined by CDER against the filed applications, it was reveled that apart from significant GMP deviations, the company falsified data and test results in approved and pending drug applications.
The AIP memorandum issued by CDER dated February 25th, 2009 says that CDER has determined that “Ranbaxy submitted untrue statements of material fact in abbreviated and new drug applications filed with the Agency. These findings concern the submission of information, such as from stability test results in support of pending and approved drug applications, from the Ranbaxy Laboratories Limited site located at Paonta Sahib”.

The AIP copy can be downloaded from here
For the benefit of readers it is worth to mention that FDA has stated in its website that

“To date, the FDA has no evidence that these drugs do not meet their quality specifications and has not identified any health risks associated with currently marketed Ranbaxy products.”