Both the EU and US have passed regulations allowing biosimilars.  You know what they are.  They are the copies of licensed drugs that have been developed by others.  Somewhat akin to the generics of the drug world.  The path to licensure of these biosimilars  is more complicated than classic drugs.  None have been licensed in the USA yet but they are off to a strong start in Europe and have been for several years where over 22 are on the market.  Link to an article written recently on the topic on Master Controls GXP Lifeline e-journal.

The link is http://www.mastercontrol.com/pharma/Biosimilars-Establishing-Themselves-Europe.html

Happy reading

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In the first quarter of 2014, there are 3 warning letters for Indian Companies.  Add to that the travails of Wockhardt and Ranbaxy over the last couple of years and it looks bleak for Indian Companies in general.  I regularly read LinkedIn Groups and I noticed a thread related the question of reliability of Indian Medicines.

Can We trust Indian  Drug Companies?

It created a firestorm of responses, many of which were from India.  The responses fell into three categories which I will paraphrase

1. The FDA is picking on us – EU and US companies have the same problems

2. I would never take an Indian medicine again

3. Indan regulators find no problem who is the FDA to tell us what our standard should be

1. Of course some US and EU and other country companies have run foul of the law. Actually there are over twice the number of warning letters directed to Pharmacies than Indian companies in Q1.  So maybe the FDA is picking on a broader range of companies.  Or putting it another way – they are doing their job and hard one it is.

2. Are all Indian companies bad?  Of course not.  I do not know the statistics but I have heard that 50% (and it could be higher or lower) of the US generics is from India and undoubtedly the major are fine (at least I hope so).

3. I am sorry but if you want to sell drugs on the US market you have to play by the rules here.  On paper, the Indian regulations are as tough as the FDAs but the question is detection of issues and enforcement that will separate the theory from the reality.

So what are the issues that are found

UVS issues appear to relate to data integrity.  Check my  previous posting on the blog .  The link to the warning letter is here. 

Smruthi Organics Ltd has a Warning Letter with only 3 observations.  One centered on data deletion, record destruction and inadequate investigations.  The link is here

Canton Laboratories Private LTD has a warning letter with 4 observations.  The essence is failure to keep data from testing, failure to actually test, failure to adequately clean equipment and failure to manufacture according to instructions and keep adequate records..  The link to the Warning Letter is here

In reality there is a lot of similarity in all these observations.  It does make one wonder about the quality of medicines.  Is this the tip of the iceberg?  Should I be worried?

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When I read FDA Warning Letters and I do often, most take the format of telling you the observations and then indicating that this is not a complete list. However, about 10% go one step further and basically read you the riot act suggesting that you need to hire a consultant to “educate you” on the errors of your ways. These are quite common.
But I believe they went to the next level for USV Limited of Mumbai. In the 2/6/2014 WL, they even listed out 7 steps for remediation. View this as reading the riot act 7 times over. Basically there was suspicion of fraud in the data.

The link is Warning Letter

They went on as follows
Get a consultant specialising in data fraud to do the following
1.) Identify the time period when the issue occurred
2.) Identify and interview employees involved in that period
3.) Identify and interview employees who have left who were employed during the period
4.) Gather data to support what comes out of the interview
5.) Trace issues to specific managers including senior management
6.) Determine if any other offending managers are in a position to influence data integrity decisions and expand your oversight
7.) Put into place procedures to prevent recurrence and assure there are no discrepancies between what was filed and reality. Create CAPAs to remedy issues. This does not apply simply to what we found but everything in essence.
Nothing revolutionary just common sense.

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The initial draft of the EU Guidance for Process Validation was released for comment and the comment period closed in October. So what has the thoughts on the new guidance since it was released? Read the linked article in Master Control on line journal for some insights.

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Pharmaceuticals are notoriously heat labile; at least many of the new high tech ones. Many require cold temperature storage at 2-8C. While they can withstand higher temperature for short periods of time, the shelf life of the products is defined by the recommended storage temperature of 2-8C.

With that understanding, is it acceptable to routinely ship them at elevated temperatures eg. ambient? Think of the money we could save says your friendly distribution staff.

This was the question posed to me recently in a webinar hosted by The Tungsten Shield Group on Cold Chain Distribution.

The European regulations are clear. The transportation temperature must be the same as the recommended storage condition. Distribution is really moving storage. Thus, a product designed as requiring cold storage, also requires the same cold condition for distribution. It is clear.

However, the FDA is particularly silent on this in regulations at least. However, they do expect transportation conditions to equal the storage conditions. Thus even the FDA does no condone this practice.

Both regulatory bodies recognize that things go wrong. A shipment heats up due to delays beyond the validated time. Patients leave the drug on the dashboard of the car for hours. These things happen. And a robust stability program designed to explore the impact of elevated temperatures can come to the rescue to determine if the abnormal conditions have degraded the product or not.

However, these accelerated conditions hsould not be used to justify a save a buck program that puts product in jeopardy.

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