Analysis of soil, land, plant, ground water and swabs to determine levels of pharmaceutical residues, supporting contamination studies and land remediation
Active pharmaceutical ingredients (APIs) entering the environment via effluent from manufacturing facilities either during operation or during decommissioning can pose a significant concern.
Our analysts support the construction and land remediation industry through analysis services focused on developing appropriate analytical methods which determine levels of APIs in soil and other environmental sample types. We have extensive experience in developing specific and cost effective methods for determining trace levels of multi-analytes within a set of samples which can reduce the overall cost of the work package for our clients. Bringing quality and safety to life, we offer Total Quality Assurance expertise to help you to meet and exceed quality, safety and regulatory standards.
Land Remediation Pharmaceutical Analysis:
- Develop and validate appropriate methods for trace levels of API or intermediates within the required sample matrix
- Critical aspects to be determined are LOD, LOQ, precision, linearity, selectivity, recovery-spiking, consistency of recovery
Pharmaceutical APIs analysis in environmental samples:
- Soil and other organic matter
- Building waste materials including concrete, brick, plaster etc.
- Swabs taken from within a manufacturing plant (we can advise as to type of swabs to use and sampling methodology)
- Ground water and water supplies
t is important to note that the above two instances are not in any manner isolated ones and the NPPA is actively considering placing more medical devices under similar price controls. Currently, there are 22 medical devices in India that are notified as drugs, out of which four are already under price controls and the rest (18) are on NPPA’s radar to be put under price control as well.
The draft National Pharmaceutical Policy 2017 (draft NPP) talks of expanding the scope of price controls. It proposes that all strengths and dosage forms of medicines in the NLEM should be subject to price caps.
Moreover, an Inter-Ministerial Committee is deliberating on a policy for Pricing of Patented Medicines and to determine a method of price negotiation that could be applied for pricing of patented medicines and medical devices before their marketing approval in India.3
In April 2017, Prime Minister Narendra Modi announced that the Government would establish a legal framework mandating doctors to prescribe medicines by their International Nonproprietary Name (INN) only.4 As per the Prime Minister, it is only with this measure that poor people would be able to access low cost medicines. This was confusing because the Indian Medical Council (Professional conduct, Etiquette and Ethics) Regulations, 20025 was already amended in 2016 to mandate that drugs be prescribed by generic names only by registered medical practitioners. However, to bolster the move to a generic market, the Government has been adopting various mechanisms for promotion of generic drugs through amendments in drug laws. To ensure quality of generic drugs approved by the State FDAs, the Union Ministry of Health (MoH) issued a notification in April 20176 requiring bio-equivalence (BE) studies to be conducted for all drugs (new or otherwise) for category II and category IV of the biopharmaceutical classification system. The draft NPP proposes mandatory bio-availability (BA) in addition to proposing to make BA/BE tests mandatory for all drug manufacturing permissions including renewals accorded by the State FDAs and the Central Drug Standards Control Organization (CDSCO), India’s drug regulator. There is also a proposal to amend the labeling regulation7 under the Drugs & Cosmetics Rules 1945 (DCR) requiring printing the generic name in at least two font sizes larger than the brand name. Additionally, the draft NPP proposes that for single ingredient drugs (except patented ones), the manufacturer would be allowed to stamp only its name on the drug package and that public procurement and dispensing of drugs will be by generic/salt names only.
Heralding these regulatory changes, the CDSCO claimed8 that it had initiated various measures in the last two years to streamline the regulatory procedures by relaxing, rationalizing, and modifying the existing provisions of the DCR, which has resulted in accelerating the regulatory approvals without compromising the safety, quality, and performance of medical products. A separate, simplified, and extensive New Drugs and Clinical Trials (CT) Rules under the Drugs and Cosmetics Act, 1940 (DCA) that will codify all amendments to date is in the planning stages. In its efforts toward digitization and implementation of the e-governance scheme, MoH launched its online licensing system called SUGAM,9 which is being continuously expanded in a phased manner. In order to give impetus to the Government’s “Make in India” initiative, emphasis is being placed on ensuring safety, efficacy, and quality of drugs manufactured in India by requiring submission of stability data and compliance of GMP/GLP practices. Additionally, there are deliberations for plugging the gaps in the sale of drugs including internet sales10 and for OTCs.
Medical Devices Rules
The Government is simultaneously in a process of streamlining the medical device industry, which has seen a paradigm shift this year with notification of separate and distinct Medical Devices Rules, 201711(MDR) effective from January 2018. The MDR has been notified with an aim to bring within its purview the entire universe of devices by notifying them as “drugs” (as defined in the DCA) in a phase-wise manner thereby bringing them within the jurisdiction of CDSCO, the drug regulator. Currently, only 22 types of medical devices are regulated in India as “drugs” under Section 3(b) (iv) of the DCA and all other non-notified medical devices do not require any registration certificate or other regulatory approvals. With the MDR and the subsequent notification of medical devices, regulatory approvals would be required. CDSCO has already circulated a draft list of 462 medical devices and 250 in vitro diagnostics (IVDs) along with their risk classification to encourage importers, manufacturers, distributors, and supply chain personnel to voluntarily adhere with the safety, performance, and quality aspects as stated in the MDR for creating the proper ecosystem for its effective implementation.12Further, deliberations are underway for developing a detailed guidance on essential principles for safety and performance to be followed in the manufacturing process of medical devices intended to be sold in India.13
Enforcing One Company, One Brand, One Molecule
The issue of the sale of the same drug under multiple brand names and different prices was first taken up in the 50th meeting of the Drug Consultative Committee held on November 4, 2016. Concerns were raised over multiple brands of the same drug (manufactured by one company and marketed by multiple companies) available at different prices. It was recommended that a separate committee be constituted to suggest measures to prevent the misuse of current practice with respect to third-party manufacturing of drugs wherein a product manufactured by a single company is marketed by multiple companies. The current draft NPP proposes to put a restraint on multiple brand names and implement the principle of one manufacturer, one salt, one brand name, and one price. In addition, the draft NPP proposes to prohibit third-party manufacturing that companies use for brand variation of the same formulation.
One of the noteworthy pieces of legislation that the Department of Pharmaceuticals (DoP) is spearheading is the Uniform Code of Pharmaceutical Marketing Practices (UCPMP). UCPMP was implemented effective January 1, 2015 as a voluntary code. The Code has provisions on gifts, hospitality, and travel that the industry allegedly extends to doctors as well as provisions on claims and comparisons, textual and audio-visual promotional material, and the conduct of sales representatives and the samples they provide to doctors. The Department is now proposing to make UCPMP statutory and mandatory under the Essential Commodities Act, 1955 along with penal provisions for companies violating the Code.
There have also been some key changes in regulations relating to Similar Biologics. On August 16, 2016, the MoH released a new Guidelines on Similar Biologics. The change to the Guidelines on Similar Biologics, 2012 seems to have been initiated in light of a suit filed in Delhi High Court by Roche against Biocon, Mylan, and the DCGI.14 Roche challenged the approval process followed during the grant of approvals for the biosimilar of Herceptin, alleging it was not in accordance with the process laid down in the Guidelines on Similar Biologics, 2012. Roche sought injunctions against Biocon and Mylan on account of imminent threat and credible apprehension of the introduction of the purported biosimilar version of the drug Trastuzumab.
The case has seen many twists with the interim order of the Single Judge of the Delhi High Court favoring Roche. The Single Judge stressed compliance of the Guidelines for Similar Biologics.15 After a detailed hearing, the Single Judge on April 25, 2016 partially allowed an interim injunction sought by Roche wherein Biocon and Mylan could market their product for only one indication even though approval was granted by CDSCO for three.
While allowing Biocon and Mylan to manufacture, market, and advertise their product under the name CANMAb, Bmab-200, or Hertraz, the order restrained them from claiming their product as “bio similar” and/ or “bio similar to HERCEPTIN, HERCLON, BICELTIS” in press releases, public announcements, promotional, or in any other print material, including labels and package inserts. It further directed Biocon and Mylan to qualify the INN name Trastuzumab used by them in their packaging as Biocon’s Trastuzumab or Mylan’s Trastuzumab and restrained them from using it as a brand name or a standalone name on cartons or package inserts.
The interim order was challenged on appeal before a Division Bench of the same Court. While the main suit is yet to be decided on the merits by the Single Bench, a Division Bench is hearing the appeal challenging the interim order dated April 25, 2016 and has virtually stayed its effect. As things stand now, both the primary suit and the cross-appeals (Roche has also filed an appeal that is being heard concurrently) are pending in respective Courts of the Delhi High Court. Since this is a case of first impression, it is expected to set an important precedent with respect to biosimilar launches in India. Some of the issues raised in the Roche vs. Biocon case had put the CDSCO in a difficult position and exposed the agency’s inability to implement the strict provisions of the earlier 2012 Guidelines.
Although the 2016 Guidelines attempt to harmonize Indian regulations in line with international standards for biosimilars, certain conditions are diluted to allow fast-tracking approval of therapies, such as widening the scope of waiver for safety and efficacy studies and the possibility of conducting such studies on fewer patients compared to international standards by ignoring scientific and statistical considerations for determining sample size.