Regulations for Abbrevated New Drug Applications

Thanks for your comments
The Drug Price Competition and Patent Term Restoration Act of 1984, usually refered to as the Hatch-Waxman Act, was designed to promote generics while leaving in tact a financial incentive for research and development. It allows generics to win FDA marketting approval by submitting bioequivelence studies (as opposed to clinical data, which is costlier to compile). It also grants a period of additional marketing exclusivity to make up for the time a patented pipeline drug remains in development. This extension cannot exceed five years, and it is in addition to the 20 years exclusivity granted by the issuance of a patent. Another provision of the Hatch-Waxman grants a 30-month stay to drug companies that file suit against generic manufactures that challenge their patents. This has become controversial in recent years, as pharmaceutical companies have used the provision to keep generics off the market by protecting their drugs with extra patents of poor quality, filing lawsuits to protect the patents even when the lawsuit will be lost, but getting the extra market exclusivity anyway. for more detail refer site:
http://www.cptech.org/ip/health/generic/hw.html

Thanks for your comment and yes its true that the Generic drug application reviewers focus on bioequivalence data, chemistry and microbiology data, requests for plant inspection, and drug labeling information.because for the bioequivalence compliance there are regulatory guidelines mentioned in 21 CFR PART 320
Reference : http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CF...
and now about the chemistry microbiology and other information there are also standard guideline that followed by the reviewer and mentioned in http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDeveloped...
and last but not the least to check the Quality and Purity of the generic drugs the reviewer inspect the plant to assure the Quality of product compliance of all guidelines cGMP, GCP etc. because at the end of this products also used for the public health care and for this main reason the reviewer strictly follow all the above parameters and infornation

thanks for your comment and the answer for your question is para filing is the "Paragraph Patent filing"
Paar I filing is made when innovator has not made the required patent information in the orange book
Para II filing for the launch of generic drugs is made when drug is already off patent
Para III filing is made when the ANDA applicant does not have any plans to sell the generic drugs until the original drug is off patent
Para IV filing is made when the ANDA applicants believes its product or the use of its product does not infringe on the innovators patents listed in the Orange book or where the applicant believes such patents are not valid. and i think after following all this procedures of filing the applicants have the minimum risk chances

Thanks for your comments and the answers are
1. The generic drugs will not at all affects the market of branded drugs because innovator product applicants already filed a patents for their product and in between this period only the branded product company is getting the 100% profit of that product and after off patent the generic drugs will be in existence But if the generic drugs are much more cost effective as well as therapeutically effective then there may be chances of affecting the market of branded drug but before this generics comes to the market only innovators are benefited otherwise the generic drugs will not be affect so much of the market of branded drugs
2.I am trying to give this answer yes of course if the company having the patent of NCE of a particular strength then also the same company can come up with the same NCE but with different strengths and also if it is in tablet for then the same company can modify the formulation such as suspension or pediatric dosage forms or transdermal or any other routes so by this way the company is using its own molecule for developing the newer formulations also and managing the cost of development because all discovery developments and safety and efficacy data is with the company only and on the other side company will be improving the reputation in the market with newer products which can be available in the market with the generic one but the generic drug is of only 1 type as the first product so obviously the company is in the competition with the leading position than the other one
I hope you will be satisfy with these answer but then also u have any query then always welcome

Thanks for your comment and answer is
The FDA has significant concerns about potential contamination, including cross-contamination, of biotech products.Discussing compliance requirements and expectations requires clarity in defining terms.
The generic drug regulatory affairs environment is relatively fast-paced in terms of regulatory writing, document compilation, marketing application (ANDA, 505(b)(2)) submissions and general regulatory correspondence.In 1984 the Drug Price Competition and Patent Term Restoration Act changed the regulatory climate for generic drugs. This law allowed for the approval of generic «me-too’ copies of many approved drug after the patent had expired. Although the road has not been smooth, the generic drug approval process has had a significant impact on the availability of generic versions of approved drug. This article discusses the evolution and changes that have occurred in generic drug approvals since the 1984 Act.
Regulatory affairs carries a set of core competencies expected of its professionals, regardless of the industry sector, organization or specific scope involved. Some of the most important of these are the ability to:
1. think both analytically and conceptually
2. understand and distill complex concepts or scenarios into manageable components
3. communicate effectively
4. operate with an understanding of the big picture (understand the impact of strategic regulatory decisions on the product and on the overall firm)
Coursework in any of the basic or medical sciences, law or business—including any exposure to healthcare topics, public health and disease management—are of value for most regulatory positions.
The regulatory associate may also become very familiar with the Orange Book and associated patent certifications (i.e., paragraph IV1) for ANDA submissions, in contrast to the innovator environment where this is not the focus.
To meet the statutory standards for marketing authorization in the US, the innovator drug must prove that the product in question is safe, effective, manufactured under appropriate quality controls and labeled according to the available data.
The strictly generic firm is not involved with the discovery or preclinical or clinical testing of a molecule (aside from bioequivalence studies, where necessary).The firm needs to prove that its products meet the appropriate standards for manufacturing and controls (the same standards as for the reference listed drug), labeling and, where applicable, bioequivalence.

Thanx for your comment and yes of course regulatory authorities plays an important role in this area and there are standard guidelines for conducting submitting and getting approval of ANDA from regulatory few links are here
http://cdsco.nic.in/html/BEGuidelinesDraftVerMarch2016,2005.pdf
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CF...

Thanx for your comment and the answer for your Q. is yes there are many antibiotics, antimalarial, Vitamins and nutrients suppliments and all the other categories available as generics in the market and they all drugs are beneficial. See the generic also contained the same active ingredients with all the other same parameters only the difference is it is marketed after the patent expiration of innovators drugs and generics are also Bioequivalents to the innovators drugs so as like branded drugs generics are also beneficial.
If you have any Query then always welcome

Thnx for ur comments and the answers for your Questions are
1. the innovator product is the one that the NCE which is patented by the Pharma company and has the all the patent rights the innovator product is completely new molecule in the market.
2. 0.1 N HCl or Simulated Gastric Fluid USP without enzymes; (2) a pH 4.5 buffer; and (3) a pH 6.8 buffer or Simulated Intestinal Fluid USP without enzymes.
Reference: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati...
3. the dissolution parameter for comparison is similarity factor f2
Reference: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformati...
http://bebac.at/lectures/1-Dissolution.pdf
4. When comparing the test and reference products, dissolution profiles should be compared using a similarity factor (f2). The similarity factor is a logarithmic reciprocal square root transformation of the sum of squared error and is a measurement of the similarity in the percent (%) of dissolution between the two curves. As we know that similarity factor used to compare the equivalence between the test ans the reference products the percentage coefficient of variance in test and reference formulations at each time point is considered for the Weight calculation. The use of this new approach is recommended in deciding the equivalence of test product with the innovator product. If the value of f2 is greater then 50 then we may surely conclude that product shows dissolution similarity and this approach may become a strong point in ANDA submission
Reference: http://www.ijpsonline.com/temp/IndianJPharmSci712142-914392_023223.pdf
I hope you will be satisfy with my answers i am trying to give this answers as per my knowledge if you know something more than this then let me also know the thing

Thanx for your comment but i know the class I, class II, class III of the medical devices not for the drugs so sorry for your Question but still i am searching the answer because its new for me also and very interesting so right now i can't tell you any thing about this Question

Thanx for your comment and yes there is a need of generic drugs in market although all the parameters were same but still we need generics because the first thing is large population in our country so only the innovator company can not satisfy the all need and the second important thing is the cost benefit of generics branded drugs are more costlier than these and it can not be affordable by all classes of people in every countries so for that reasons the generics are needed

Dear Bhaskar

Thanx for your comment the answers are

1. the difference between the patent and the exclusivity is the time difference patents expire 20 years from the date of filing and the exclusivity depend on types of it means as i mentioned in slides as for orphan drugs its different, for NDA, for Pediatrics etc. and the second thing is Patents are granted by the patent and trademark office whereas Exclusivity is exclusive marketing rights If the patent period has expired, or there is no patent on a product, data exclusivity will act independently to delay the entry of any generic
companies wishing to enter the market until the period of data exclusivity is over. However, the data exclusivity right is a much stronger right than a patent because, unlike patent law, there are no exceptions or flexibilities that allow governments to tailor the law to national circumstances.
2. About this question i am also not sure but still i am trying to answer it Patents and exclusivity may or may not run concurrently and may or may not encompass the same claims. if you have any idea about this then let me also know that
3. Not only branded drug but also the generics also pass through strict regulations to enter the market and if the innovator drug is not available in market then how can make it generics because innovator is the base of the generics and drug trial are necessary for the innovator drugs so we can't directly start from the generics unless and until we have the baseline for that. After all branded or innovator drugs are the king of the market till the patent is over
I hope you will get my points and regarding the 2 Q i am also not known completely so if you have the answer then tell me also
Thank you once again

Hi Shobha

Thanx for your comments and questions
1. the parameters consider in Bioequivalence studies are Cmax, Tmax half life of drug, AUC, Kel, %CV, AUCinf, and AUCt these all Pharmacokinetic parameters are to be considered
2. there are no any direct guideline stating as for development of generic drugs but yes generic drug research in humans is also considered as a part of clinical trial so for this reason any guideline regarding the conductance, submission, documentation, reporting an adverse events and many more are followed from the ICH only E1 , E2:-Clinical Safety E3:- Clinical Study Reports,E6:-Good Clinical Practice E8:-GENERAL CONSIDERATIONS FOR CLINICAL TRIALS, E9:-STATISTICAL PRINCIPLES FOR CLINICAL TRIALS etc
3. yes there is need of QA in generic development because at the end of the day the generic as well as the branded product reaches to the patients and the patients safety is our prime job so for that reason quality assurance is to be needed
4. Merck & Co.'s, InvaGen Pharmaceuticals, Sandoz,Matrix, Astra Zeneca, GSK, Cipla, Teva Pharmaceutical,Novartis, Johnson & Johnson, Dr. Reddy, Glenmark, Ranbaxy, Zydus Cadila, Torrent, Jubilant, Sun Pharma, Pfizer and many more
5. the temperature,humidity for the stability studies necessary for the generic developement are the same as the innovator drug because in case generic only the excipents gets changed not API the strength of the API is also equivalent to the innovator drug and for this reason the temp. humidity and all other parametres for the stability study are same as per the innovator and the API
6.can u elaborate your last Question I didn't get it rightly can you tell me what exactly u want to know?
I hope you will be satisfy with my answers if not then keep asking you are always welcome

Hi Noopur ,

First of all thanx and yes there are some reasons to refuse the ANDA application and these reasons are
1 the very first criteria is Bioequivalenece if the two product are not equivalent in their bioavailability, Theraprutically
2 second is the adverse events of that generic drug if the generic drug is showing more adverse events than the marketed one then it must be the reason of refusal
3 the subject variability if the action of drug is variable in different subjects then it may affect the BA as well as BE
4 If the FDA or any regulatory authority have any doubt about the conduct , any documents or any other ethical issue of the study then it may not get approval
5 and even after marketing if the drug showing many serious adverse event then it may refuse because after marketing also the sponsor company have to perform the periodic safety update reports (PSUR) and it is submitted to FDA or any respective regulatory body for the first 2 years
Hi hope I resolve your Queries if any other then always welcome

Exclusive Marketing Rights

Dear Pankaj

This new provision has been incorporated in the Patents Act, 1970 as amended by The Patents (Amendment) Act, 1999 with effect from 1st January, 1995. Under this amendment to the Patents Act, 1970 it is now possible to make an application for patent claiming for a substance itself intended for use or capable of being used as Medicine or Drug, excepting the intermediate for the preparation of drug. However that India has the privilage, under WTO regime, of a ten years transition period. Thus application for product claims for medicine or drug will not be processed until the end of 2004. But Exclusive Marketing Rights (EMR) can be obtained for that application if certain conditions as stated below are fulfilled:

1.Where an invention has been made in India or outside India and before filing such a claim in India, application for the same invention claiming identical article or substance in a Convention Country (WTO) has been filed on or after 1st January, 1995 and a patent has been granted on or after the date of making a claim for article or substance in India and approval to sell or distribute has been obtained in the said Convention Country on the basis of the test done on or after 1st January, 1995.
2.Where an invention has been made in India and before filing such a claim the applicant has made an application for patent on or after 1st January, 1995 for method or process of manufacturing the identical article or substance and patent has been granted in India on or after the date of making of the product claim.
3.Marketing approval of the article or substance has been obtained from the appropriate authority in India provided that the application for patent has not been rejected by the Controller on the basis of the report of the Examiner that the invention is not an invention (Section - 3) or the invention is an invention on which no patent can be granted (Section - 4).

Duration

EMR will be valid for a period of five years or till the date of grant of the patent or date of rejection of the application for the grant of patent whichever is earlier. for more information refer http://www.patentoffice.nic.in/ipr/patent/patents.htm

Hi,
It's not necessary that generics are always of low Quality but obvious the intention of generic product is to be available at low prize for the all. there are many MNC are also making the generics and having a good quality as well as market value Its not like that the generics are always manufactured by small scale.
the second thing is in generic production the research expenses reduces so for that reason only they are at low prize and because of all drug development and research cost the innovative drug is expenses and it can not be possible to afford by a common people in India so for that more generics are their in Indian market and last but not the least about the quality yes their are FDA's strict regulation for the Quality checks of the generics also because they treated all products are equally so obviously Quality checking must be their
I hope you'll get my point as per my knowledge i had try to resolve your Queries but if still you any doubt then always welcome and if you know some more about this topic then let me know that then I'll also get some more info
Thanx for your comment.