Re: Quality Of Medicines

October 29, 2008

Dear Dr.Srisailam,There are only a handful of labs which are accredited for such puproses. The Government will accept only those results from government labs which are hopelessly understaffed and ill equipped to deal with the large number of samples. (Mashlkar's report clearly states this problem) On the few times when samples have been sent the report comes back after one year - by which time the medicines have been consumed since we cannot afford to stock more than 3-4 months quantity. Perhaps the only way to deal with this is to set up our own analysis labs - starting in a small way and slowly building up to have sophisticated equipment.

Posting on the web is much easier - you need to have a few web-wise students who will be happy to do it. The impact it will have will be much bigger and we will force the manufacturers to clean up their act.Sincerely

GitanjaliOn Thu, Oct 30, 2008 at 10:09 AM, Dr. Keshetti Srisailam <ksrisailam@...> wrote:

Dear Dr. Gitanjali

I do accept your concern regarding the quality of medicines

I find many government hospitals supplying medicines free of cost that are of poor in their quality.

With the help of a pharmaceutical or biomedical analysis laboratory one can assess them in respect to their content variability

I welcome your website posting of suppliers' names

But how many hospitals do such postings?

Dr. Srisailam K

From: Dr.B.Gitanjali <gitabatman@...>

Subject: quality of medicines

netrum

Date: Thursday, 30 October, 2008, 6:50 AM

Hi to all netrum users!

I am Gitanjali. At present working as Professor of Pharmacology at

JIPMER Pondicherry. I also am the officer-in-charge of the Hospital

Pharmacy. Since JIPMER issues free medicines to all its patients

medicines are procured through an annual tender. We have put in

place some quality indicators - such as the company should have WHO-

GMP certification, at least three years market standing for the

product, non- conviction certificate etc.,

However, the medicines we get are far from satisfactory (quality -

wise). The WHO-SEARO funded the Dept. of Pharmacy for a unique

project wherein all quality issues are put up on the website of

JIPMER. We hope that this will help us share the information on

suppliers of poor quality drugs so that other hospitals need not

purchase medicines from the same manufacturers.

I would like NETRUM users to please visit www.jipmer.edu and visit

pharmacy. Every patient depending on hospitals like ours to provide

medicines has the right to get good quality medicines. It should be

our mission to ensure that they do.

Get your preferred Email name!

Now you can @ymail.com and @rocketmail.com.

http://mail.promotions./newdomains/aa/

-- Dr.Gitanjali Batmanabane MD PhDProfessor of Pharmacology & Officer-in-charge,Dept. of PharmacyJawaharlal Institute of Postgraduate Medical Education & Research

Pondicherry 605 006India

October 30, 2008

Dear Gitanjli,

We have had one such experience here in Pakistan and it didn't work the way we thought. We imported a ready made mini laboratory from Germany and had been testing the market available brands for quality. But unfortunately it gives only very basic information about the quality of drug, and even if you are sure for yourself, it is hard for you to prove it to others, and almost impossible to prove it to the industry. What you may need is a bit advanced laboratory set up where authentic monographical testing can be performed.

Just wanted to share an experience so that you have it in mind while you go any further.

Regards,

Tauqeer

TAUQEER MUSTAFA CHOUDHRY.

B.Pharm, MPH

Punjab Lok Sujag

Lahore

From: Gitanjali Batmanabane <gitabatman@...>netrum Sent: Thursday, October 30, 2008 5:37:56 AMSubject: Re: quality of medicines

Dear Dr.Srisailam,There are only a handful of labs which are accredited for such puproses. The Government will accept only those results from government labs which are hopelessly understaffed and ill equipped to deal with the large number of samples. (Mashlkar's report clearly states this problem) On the few times when samples have been sent the report comes back after one year - by which time the medicines have been consumed since we cannot afford to stock more than 3-4 months quantity. Perhaps the only way to deal with this is to set up our own analysis labs - starting in a small way and slowly building up to have sophisticated equipment.Posting on the web is much easier - you need to have a few web-wise students who will be happy to do it. The impact it will have will be much bigger and we will force the manufacturers to clean up their act.SincerelyGitanjali

On Thu, Oct 30, 2008 at 10:09 AM, Dr. Keshetti Srisailam <ksrisailam (DOT) com> wrote:

Dear Dr. GitanjaliI do accept your concern regarding the quality of medicinesI find many government hospitals supplying medicines free of cost that are of poor in their quality.With the help of a pharmaceutical or biomedical analysis laboratory one can assess them in respect to their content variabilityI welcome your website posting of suppliers' namesBut how many hospitals do such postings?Dr. Srisailam KFrom: Dr.B.Gitanjali <gitabatmangmail (DOT) com>Subject: quality of medicinesnetrumgroups (DOT) comDate: Thursday, 30 October, 2008, 6:50 AM

Hi to all netrum users!I am Gitanjali. At present working as Professor of Pharmacology at JIPMER Pondicherry. I also am the officer-in-charge of the Hospital Pharmacy. Since JIPMER issues free medicines to all its patients medicines are procured through an annual tender. We have put in place some quality indicators - such as the company should have WHO-GMP certification, at least three years market standing for the product, non- conviction certificate etc.,However, the medicines we get are far from satisfactory (quality - wise). The WHO-SEARO funded the Dept. of Pharmacy for a unique project wherein all quality issues are put up on the website of JIPMER. We hope that this will help us share the information on suppliers of poor quality drugs so that other hospitals need not purchase medicines from the same manufacturers.

I would like NETRUM users to please visit www.jipmer.edu and visit pharmacy. Every patient depending on hospitals like ours to provide medicines has the right to get good quality medicines. It should be our mission to ensure that they do. Get your preferred Email name!Now you can @ymail.com and @rocketmail.com. http://mail. promotions. / newdomains/ aa/-- Dr.Gitanjali Batmanabane MD PhDProfessor of Pharmacology & Officer-in-charge,Dept. of PharmacyJawaharlal

Institute of Postgraduate Medical Education & ResearchPondicherry 605 006India

October 31, 2008

Dear Dr. Bachewar,

Could you repeat please. My monitor shows some symbols which are unreadable. only locost is seen.

Sincerely

Gitanjali

On Thu, Oct 30, 2008 at 8:37 PM, naren bachewar <naren_bachewar@...> wrote:

Hello madam and all,I had somewhere heard about & #39;LOCOST & #39; organisation.Are they just concerned about lower cost, or also about quality of medicine.. Can you please through light on it?

Dr. Narendra Bachewarlecturer in pharmacology,ACPM MC, Dhule.Connect with friends all over the world. Get India Messenger at http://in.messenger./?wm=n/

-- Dr.Gitanjali Batmanabane MD PhD

Professor of Pharmacology & Officer-in-charge,Dept. of PharmacyJawaharlal Institute of Postgraduate Medical Education & ResearchPondicherry 605 006India

October 31, 2008

Hello madam,

AS I AM POSTING FROM MY MOBILE, IT IS QUITE POSSIBLE THAT THE FONTS ARE NOT

MATCHING.

I WANTED TO KNOW ABOUT, IF & #39;LOCOST & #39; IS CONCERNED ABOUT QUALITY OF

MEDICINES OR ONLY ABOUT COST?

DR. THAWANI HAS FORWARDED MY MAIL TO THE RESPECTED AUTHORITY.

Dr. NARENDRA BACHEWAR

Gitanjali Batmanabane wrote:

> Dear Dr. Bachewar,

> Could you repeat please. My monitor shows some symbols which are unreadable.

only locost is seen.

> Sincerely

> Gitanjali

> On Thu, Oct 30, 2008 at 8:37 PM, naren bachewar < naren_bachewar@ .co.

in > wrote:

> Hello madam and all, I had somewhere heard about & #39;LOCOST & #39;

organisation. Are they just concerned about lower cost, or also about quality of

medicine.. Can you please through light on it?

> Dr. Narendra Bachewar lecturer in pharmacology, ACPM MC, Dhule. Connect with

friends all over the world. Get India Messenger at http://in.messenger

../ ?wm=n/

> -- Dr.Gitanjali Batmanabane MD PhD

> Professor of Pharmacology & Officer-in-charge, Dept. of Pharmacy Jawaharlal

Institute of Postgraduate Medical Education & Research Pondicherry 605 006 India

>

Get perfect Email ID for your Resume. Grab now

http://in.promos./address

October 31, 2008

Hi Narendra,

I know the activists who are managing LOCOST at Vadodara. Since the

question specifically concerned them, I have asked them to reply to

your concern. Even though I know about their services, it will be

better to hear straight from them in this matter.

Vijay

> > Hello madam and all, I had somewhere heard about

& #39;LOCOST & #39; organisation. Are they just concerned about lower

cost, or also about quality of medicine.. Can you please through

light on it?

> > Dr. Narendra Bachewar lecturer in pharmacology, ACPM MC, Dhule.

Connect with friends all over the world. Get India Messenger

at http://in.messenger ./ ?wm=n/

> > -- Dr.Gitanjali Batmanabane MD PhD

> > Professor of Pharmacology & Officer-in-charge, Dept. of Pharmacy

Jawaharlal Institute of Postgraduate Medical Education & Research

Pondicherry 605 006 India

> >

>

> Get perfect Email ID for your Resume. Grab now

http://in.promos./address

>

November 1, 2008

Hi Gitanjali,

I had a different query on drug quality from a clinician's perspective.

As a physician in a private medical college I feel I waste a lot oftime listening to more than 10 different medical reps extolling thevirtues of just one single generic and I have no means to reallyfigure out if there is at all any difference in quality.

Do you recommend any particular decision making strategy for this ageold problem confronting clinicians?

warm regards,

rakesh

Rakesh Biswas MDProfessor,Department of Medicine,People's college of medical sciences,Bhopal-462010 (M.P.) IndiaTel & Fax: +91 - 755 - 4005210, 4005211Mob: +919755619861Email: rakesh7biswas@...

On 11/1/08, Gitanjali Batmanabane <gitabatman@...> wrote:

Dear Dr. Bachewar,

Could you repeat please. My monitor shows some symbols which are unreadable. only locost is seen.

Sincerely

Gitanjali

On Thu, Oct 30, 2008 at 8:37 PM, naren bachewar <naren_bachewar@...> wrote:

Hello madam and all,I had somewhere heard about & #39;LOCOST & #39; organisation.Are they just concerned about lower cost, or also about quality of medicine.. Can you please through light on it?

Dr. Narendra Bachewarlecturer in pharmacology,ACPM MC, Dhule.Connect with friends all over the world. Get India Messenger at http://in.messenger./?wm=n/

-- Dr.Gitanjali Batmanabane MD PhDProfessor of Pharmacology & Officer-in-charge,

Dept. of PharmacyJawaharlal Institute of Postgraduate Medical Education & ResearchPondicherry 605 006India

November 1, 2008

Hi allDear Gitanjali...nice to have you on NetRUM. I was looking forward to this discussion.I agree with Vijay..In fact we need to go into the genesis of this " fear Factor " wrt generics. While quality and cost by and large are directly proportional.it does not limit the use of anything that comes cheap. If we could " promote " generics in an authentic manner, the scenario might be different.

Chetna2008/11/1 Vijay <drvijaythawani@...>

Generics and quality of medicines

Hi,

Currently this issue is also being discussed on E-drug because

recently Kenya has proposed the draft to ban generics in their country

because they fear counterfeits. Counterfeits and substandard /poor

quality medicines are different issues. Banning generics is no

solution for solving counterfeit problem.

In our part of the world, often doctors and patients ask questions

about the quality of generics and hence do not promote generics. I

purchase and use " branded generics " (the third category from branded,

generic and branded genric classification as it exists in India)

personally and for my family and have no complaints.

The fear psychosis about quality of generics is built in our psyche.

Karnataka and Delhi Governments procure generics at cheapest prices in

India. We buy generics for our Govt hospitals. If the quality of

generics was indeed that bad as feared then the condition of patients

consuming these would have deteriorated but it is not so.

Vijay Thawani

-- Dr Chetna DesaiDepartment of PharmacologyB. J. Medical CollegeAhmedabad 380016Visit http://www.pharmacologybjmc.org

http://pharmacbjmc.110mb.comwww.poliofoundation.org

November 1, 2008

Dear Dr.Rakesh,

You have actually posed two questions. I will answer the easier one first :-)

(1) Waste of time listening to medical reps - if you feel medical reps are indeed taking up a lot of your time you should inform them to leave their promotional literature with your secretary and leave or tell them when you will meet with them, say one hour a week or whatever. I have a notice outside my lab informing reps of the days of the week on which I will see them and the time. They often do not bother about it, and come as they please (after profusely apologizing) - and I refuse to see them (also after profusely apologizing) if I have other work to do. So, at least you can still feel you are in charge of your time.

(2) How to recognize superior quality - I have no answers to that. If you pick one which is less costly and know it works - you can stick with it. The initial sifting and checking for cost you may have to do, but I have no ready made answers for this question. I also believe it is better not to trust those drugs with more than one ingredient (other than the approved fixed dose drug combinations) - it is a favourite ploy of companies to say we have added this ingredient to improve absorption, delay excretion and so on without actual proof.

Sincerely

Gitanjali

On Sat, Nov 1, 2008 at 1:03 PM, Rakesh Biswas <rakesh7biswas@...> wrote:

Hi Gitanjali,

I had a different query on drug quality from a clinician's perspective.

As a physician in a private medical college I feel I waste a lot oftime listening to more than 10 different medical reps extolling thevirtues of just one single generic and I have no means to reallyfigure out if there is at all any difference in quality.

Do you recommend any particular decision making strategy for this ageold problem confronting clinicians?

warm regards,

rakesh

Rakesh Biswas MDProfessor,Department of Medicine,People's college of medical sciences,Bhopal-462010 (M.P.) IndiaTel & Fax: +91 - 755 - 4005210, 4005211Mob: +919755619861Email: rakesh7biswas@...

On 11/1/08, Gitanjali Batmanabane <gitabatman@...> wrote:

Dear Dr. Bachewar,

Could you repeat please. My monitor shows some symbols which are unreadable. only locost is seen.

Sincerely

Gitanjali

On Thu, Oct 30, 2008 at 8:37 PM, naren bachewar <naren_bachewar@...> wrote:

Hello madam and all,I had somewhere heard about & #39;LOCOST & #39; organisation.Are they just concerned about lower cost, or also about quality of medicine.. Can you please through light on it?

Dr. Narendra Bachewarlecturer in pharmacology,ACPM MC, Dhule.Connect with friends all over the world. Get India Messenger at http://in.messenger./?wm=n/

-- Dr.Gitanjali Batmanabane MD PhDProfessor of Pharmacology & Officer-in-charge,Dept. of PharmacyJawaharlal Institute of Postgraduate Medical Education & ResearchPondicherry 605 006

India

-- Dr.Gitanjali Batmanabane MD PhD

Professor of Pharmacology & Officer-in-charge,Dept. of PharmacyJawaharlal Institute of Postgraduate Medical Education & ResearchPondicherry 605 006India

November 2, 2008

Dear Vijay Sir

Greeting from Ram

I am completely agree with you, but the question again is wheter our DRA is capable and competent enough to do it or not? if yes whether they are doing the right things which is suppose to be done by them or not? What is the penalty mechanism in India and other part of the world for non complaince of the duty adn responsibilities of the relevant agency.

Couple of month ago, in Nepal a Minister locked one govenment official in TOILET as penalty for non complaince of their duty and suspected to be involved with the related curruption. But it was in other sector, the health sector is more sensative these days and linked to daily lives.

Yours

Ram C Sah

From: Vijay <drvijaythawani@...>netrum Sent: Saturday, November 1, 2008 11:48:41 PMSubject: Re: Quality of medicines

Hi Ram,Commissions, cuts, offers, incentives, schemes, discounts, sponsorships etc; are indulged in pharmaceutical marketing.Ethically these should not affect the quality of the medicines.To ensure requisite quality of pharmaceutical products is responsibility of the DRA. If the DRA fails to discharge its duty sincerely and honestly or is greased to look the other side then the quality of medicines can not be assured. Hence are required the public pressure groups, the watch dogs, who should have the courage of conviction to stand up and take an enlightened stand in the matter. NetRUM is one such platform.Vijay > > From: Vijay <drvijaythawani@ ...>> Subject: Quality of medicines: Banning generics ?> netrumgroups (DOT) com> Date: Saturday, November 1, 2008, 11:33 AM> > > > > > > Hi,> I am copying my post from E-drug, as fair use.> Vijay Thawani> ------------ --------- --------- --------- --------- ------> E-DRUG: MSF Briefing document on Kenya's 2008 Anti-Counterfeit Bill > (2)>

------------ --------- --------- --------- --------- ------> Hi,> > I agree to the enlightened stand of MSF that counterfeits and > substandard/ poor quality medicines are clearly two different > issues. Where as counterfeits certainly need to be banned, action is > also desired against the substandard medicines. But banning > counterfeits does not mean banning all generics in the country. Such > misguided contention will result in selective, intentional > proliferation of branded medicine industry in the country. This way > the country will be playing into the hands of branded medicine > industry and sacrificing the paramount interest of its citizenry. > Such proindustry policy is antipatient in terms of medicine > affordability which in turn affects the accessibilty to medicines. > > What are Kenyan medical doctors, medical association,

medical > activists, NGOs and pressure groups doing? Allowing smooth induction > of such antipatient law?> > May the better sense prevail.> > Dr Vijay Thawani, India > vijaythawani@ rediffmail. com>

November 2, 2008

Dear Gitanjali and all,

Nice to have you as moderator in this forum.

Your experience in this subject will help many of us. Can you share some of the issues associated with generics/ medicines available at general hospitals?

The medicines are purchased through tender system, which has the advantage of favouring competition and reducing the cost .However,the main drawback of this system is quality is not given the priority over cost considerations. The price quoted by bidder is so less which raise the doubt about the quality of the product. How do you deal with this situation ? Can you evaluate the quality just by having GMP certificate?

Mira Desai

From: Dr.B.Gitanjali <gitabatman@...>Subject: quality of medicinesnetrum Date: Thursday, 30 October, 2008, 6:50 AM

Hi to all netrum users!I am Gitanjali. At present working as Professor of Pharmacology at JIPMER Pondicherry. I also am the officer-in-charge of the Hospital Pharmacy. Since JIPMER issues free medicines to all its patients medicines are procured through an annual tender. We have put in place some quality indicators - such as the company should have WHO-GMP certification, at least three years market standing for the product, non- conviction certificate etc.,However, the medicines we get are far from satisfactory (quality - wise). The WHO-SEARO funded the Dept. of Pharmacy for a unique project wherein all quality issues are put up on the website of JIPMER. We hope that this will help us share the information on suppliers of poor quality drugs so that other hospitals need not purchase medicines from the same manufacturers. I would like NETRUM users to please visit www.jipmer.edu and

visit pharmacy. Every patient depending on hospitals like ours to provide medicines has the right to get good quality medicines. It should be our mission to ensure that they do.

Add more friends to your messenger and enjoy! Invite them now.

November 4, 2008

Dear Mr Raj Vaidya

Thank you very much for a detailed description of the facts.

My concern is regarding

Brand of a company known to be reliable/reputed

How can we monitor, if say a big pharma house is getting its branded generic manufactured from a small pharma company in Baddi (HP) and some how mixing it with the other lot...

I mean do will we call it contract manufacturing as this is not registered any where

I think this also an important issue which is not much talked about.. .

Regards

Varun Gupta

Dr Varun Gupta Resident Department of Pharmacology JNMC AMU Aligarh 09358312925 varunpgupta@...

From: DIC Goa <dicgoa@...>Subject: Quality Of Medicinesnetrum Date: Tuesday, November 4, 2008, 9:56 PM

Hello !

I will try to throw some light on Quality of medicines and prescribers' dilemma :

In developed countries, and most countries in the world :

BRAND/Branded drug is the product of the Originator company (company which discovers it).

GENERIC – is a copy of the originator Brand, BUT, which has a BA (Bioavailability) & BE (Bioequivalence) which is comparable to the BRAND. It is much cheaper than the Brand.

India is UNIQUE. The story is very different.

In common understanding, in India :

a) A Branded drug is one which has been given a Brand (Trade) name by the manufacturer company, and marketed/promoted to doctors through MRs, for their prescriptions. In reality, these are COPIES, but NOT NECESSARILY having a comparable BA or BE with the originator Brand (because it is not mandatory to do these tests most of the times).

Generic Drugs are those which generally have not been given a Trade/Brand name. They are not marketed through MRs. They are also copies, and not necessarily having comparable BA/BE.

There are a variety in type of Generics in India (not legally, but as a matter of fact) (There is overlap in the classification that I have done) :

a. Generic Generics – Do not have a Trade name. Are of 2 varieties :

i) Those produced by companies which also produce Branded (Indian) drugs (so called reputed companies).

ii) Those produced by other companies (these generally are in the business only for supplying on tender)

These are mainly produced for Govt & other public sector hospitals – to be quoted and supplied mainly on tender. Prices are very low.

b. Branded Generics – These are given a Brand/Trade name, but are NOT promoted through MRs for prescribing by doctors. They are mainly promoted to doctors & hospitals (to push/dispense/ sell to their patients), or to pharmacies (to push/dispense/ sell them across the counter). The cost to the consumer is similar to that of Branded drugs; however the cost to the doctor/pharmacy is very very low. Thus, the doctor/hospital or pharmacy which buys and pushes these can make huge profits.

So, in effect, the consumer, who pays out of pocket, whether he gets pushed the Branded drug or the Branded Generic, he has to pay almost the same (through his nose).

In the USA, ALL drugs are approved ONLY after they submit their detail data to the FDA. Thus, every drug is expected to have comparable BA & BE to the Brand.

Detail guidelines are given depending on the type of dosage form, and the drug in question, as to how to submit the BA & BE data. Some drugs are permitted to have BA BE waivers (BE proving not required), if they fall in certain classes, or for certain dosage forms. For example, the drugs which fall in the BCS Class I drugs – drugs which are highly soluble/do not have BE problems, IV solutions, etc.

(BCS = Biopharmaceutics Classification System) – Details reproduced in blue ink, from US FDA website below.

However, for NTI Drugs (Drugs with narrow therapeutic index), extra cautions are needed before a Generic is approved. In fact, it is highly recommend NOT to switch Brands/Generics once a patient starts taking a particular Brand /Generic, because there is a possibility of even the "comparable" BA & BE between the 2 Generics or Generic & Brand to fluctuate between less efficacy & toxicity.

Coming back to Indian Branded drugs, and how to choose which one to prescribe :

Since in India there is no need for BA BE studies most of the times, even though a drug passes the chemical test for drug content & DT (disintegration time), there may be no guarantee that the drug will dissolve to the rate & the extent desired, and thus absorbed in the blood stream (since for most drugs there is no need for Dissolution test & BA BE studies) ! [Except when a new drug is introduced in India – the 1st 4 to market the drug have to produce BA BE data – (I think done on 6 healthy volunteers)] – {reliability of BA BE studies done in India is I am sure a separate worthy discussion on NMetrum}

The physician thus is really at a huges dilemma as has been expressed by many Netrumians.

There could be various ways to decide which Indian Brand to prescribe :

1. Brand of a company known to be reliable/reputed

2. You have used the Brand before and are happy with its outcome.

3. For low solubility, low permeability & NTI drugs, do not take a risk trying to compromise the price too much.

One needs to do this exercise (trial & error) for a few brands, and then if satisfied with the efficacy, choose the one which is the cheapest, and stick to it.

There are reasons why this technique, (or even the technique of prescribing a costly brand of a reputed company may fail ) – especially for drugs with lower solubility or those known to have problems with BA :

Companies may change the inactive ingredients of the formulation at times, this may result in variation in BA – but you will not know of it.

Companies very often get their products manufactured in more than one factory – very often it is a SSI Unit. Same Brand manufactured in different factories may give variable BA. So, you cannot be guaranteed that even though your patient receives the same brand each time, it has a comparable BA/BE !!!!

SO, along with some techniques, one needs to hope for the best and pray too (Ram Bharose') !

Prescribing, stocking in public hospitals is even more challenging !

The Biopharmaceutics Classification System (BCS) Guidance

Office of Pharmaceutical Science

Purpose of the BCS Guidance:

Expands the regulatory application of the BCS and recommends methods for classifying drugs.

Explains when a waiver for in vivo bioavailability and bioequivalence studies may be requested based on the approach of BCS.

Goals of the BCS Guidance:

To improve the efficiency of drug development and the review process by recommending a strategy for identifying expendable clinical bioequivalence tests.

To recommend a class of immediate-release (IR) solid oral dosage forms for which bioequivalence may be assessed based on in vitro dissolution tests.

To recommend methods for classification according to dosage form dissolution, along with the solubility and permeability characteristics of the drug substance.

According to the BCS, drug substances are classified as follows:

Class I - High Permeability, High SolubilityClass II - High Permeability, Low SolubilityClass III - Low Permeability, High SolubilityClass IV - Low Permeability, Low Solubility

CLASS BOUNDARIES

A drug substance is considered HIGHLY SOLUBLE when the highest dose strength is soluble in < 250 ml water over a pH range of 1 to 7.5.

A drug substance is considered HIGHLY PERMEABLE when the extent of absorption in humans is determined to be > 90% of an administered dose, based on mass-balance or in comparison to an intravenous reference dose.

A drug product is considered to be RAPIDLY DISSOLVING when > 85% of the labeled amount of drug substance dissolves within 30 minutes using USP apparatus I or II in a volume of < 900 ml buffer solutions.

SOLUBILITY DETERMINATION

pH-solubility profile of test drug in aqueous media with a pH range of 1 to 7.5.

Shake-flask or titration method.

Analysis by a validated stability-indicatin g assay.

PERMEABILITY DETERMINATION

Extent of absorption in humans:

Mass-balance pharmacokinetic studies.

Absolute bioavailability studies.

Intestinal permeability methods:

In vivo intestinal perfusions studies in humans.

In vivo or in situ intestinal perfusion studies in animals.

In vitro permeation experiments with excised human or animal intestinal tissue.

In vitro permeation experiments across epithelial cell monolayers.

DISSOLUTION DETERMINATION

USP apparatus I (basket) at 100 rpm or USP apparatus II (paddle) at 50 rpm.

Dissolution media (900 ml): 0.1 N HCl or simulated gastric fluid, pH 4.5 buffer, and pH 6.8 buffer or simulated intestinal fluid.

Compare dissolution profiles of test and reference products using a similarity factor (f2).

BCS BIOWAIVER

Rapid and similar dissolution.

High solubility.

High permeability.

Wide therapeutic window.

Excipients used in dosage form used previously in FDA approved IR solid dosage forms.

REQUEST FOR BIOWAIVERS

Data Supporting Rapid and Similar Dissolution

A brief description of the IR products used for dissolution testing.

Dissolution data obtained with 12 individual units of the test and reference products at each specified testing interval for each individual dosage unit. A graphic representation of the mean dissolution profiles for the test and reference products in the three media.

Data supporting similarity in dissolution profiles between the test and reference products in each of the three media, using the f2 metric.

Data supporting High Permeability:

For human pharmacokinetic studies, information on study design and methods used along with the pharmacokinetic data.

For direct permeability methods, information supporting method suitability with a description of the study method, criteria for selection of human subjects, animals, or epithelial cell line, drug concentrations, description of the analytical method, method to calculate extent of absorption or permeability, and information on efflux potential (if appropriate) .

A list of selected model drugs along with data on the extent of absorption in humans used to establish method suitability, permeability values and class for each model drug, and a plot of the extent of absorption as a function of permeability with identification of the low/high permeability class boundary and selected internal standard.

Permeability data on the test drug substance, the internal standards, stability information, data supporting passive transport mechanism where appropriate, and methods used to establish high permeability of the test drug substance.

Data supporting High Solubility:

Description of test methods (analytical method, buffer composition) .

Information on chemical structure, molecular weight, nature of drug substance, dissociation constants.

Test results summarized in a table with solution pH, drug solubility, volume to dissolve highest dose strength.

Graphical representation of mean pH-solubility profile.

Raj Vaidya

Community Pharmacist

Panaji - Goa

November 4, 2008

Dear Dr Varun,

COntract manufacturing is perfectly legal, and done with due FDA permission & formalities.

This lot has a separate Batch no, and the label says where it is manufactured, etc.

COmpanies try and take care that quality in terms of the content of the drug present in the dosage form is maintained.

But the question of BA & BE may not be addressed. It may not be a problem with drugs having no BA problems.

THen there are pressures from marketing Dept. to increase production to high levels, pressures to release the drugs in the market even before they are tested and certified by their Quality COntrol Dept, quality compromises & short cuts in manufacturing so that production rates are increased, etc.

SOme of the stories we hear from what is happenning on the production floor are quite horrendous !

All the drugs exported to USA, EU are done in manufacturing facilities which are certified by these agencies, and particular care and procedures followed. However, the latest controversy & soup which Ranbaxy got into with US FDA was becaus there is suspicion that these procedures were not carefully followed.

For drugs supplied to the Indian market, these stringencies need not be followed ! SImply because our Indian FDA requirements are not so stringent !

India has the honour of having the maximum number of US FDA mfg units outside the USA - all the drugs manufactured in these units are meant for supply to USA, and not India !

Raj

On 11/4/08, varun gupta <varunpgupta@...> wrote:

Dear Mr Raj Vaidya

Thank you very much for a detailed description of the facts.

My concern is regarding

Brand of a company known to be reliable/reputed

How can we monitor, if say a big pharma house is getting its branded generic manufactured from a small pharma company in Baddi (HP) and some how mixing it with the other lot...

I mean do will we call it contract manufacturing as this is not registered any where

I think this also an important issue which is not much talked about.. .

Regards

Varun Gupta

Dr Varun Gupta Resident Department of Pharmacology JNMC AMU Aligarh 09358312925 varunpgupta@...

From: DIC Goa <dicgoa@...>Subject: Quality Of Medicines

netrum Date: Tuesday, November 4, 2008, 9:56 PM