A roundup of developments and the latest news from China (Cipla, Jiangsu Acebright, Sun Pharma), Europe (European Medicines Agency, Swissmedic), India (Dr. Reddy’s Laboratories, Emcure Pharmaceuticals, Natco Pharma), Israel (Mapi Pharma), and Kuwait (Mezzan Holdings).

China

Cipla EU and Jiangsu Acebright To Invest $30 Million in Joint Venture Company in China

Cipla EU, part of the Mumbai,India-headquartered company, Cipla, and Jiangsu Acebright, a supplier of anti-viral and oncology products and vitamin ingredients, have partnered to form a joint venture company in China, with a combined investment of $30 million. Cipla says upon closing, the new company will set up a manufacturing facility for local manufacture of respiratory products.

Under the agreement, the new company will become a subsidiary of Cipla. Cipla will hold an 80% stake, and Acebright will hold a 20% stake for a combined total investment of $30 million.

Jiangsu Acebright Pharmaceuticals is a subsidiary of the Shanghai Acebright Pharmaceuticals Group.

Source: Cipla

Sun Pharma and China Medical System Holdings to Develop Generics for China

Sun Pharmaceuticals, a Mumbai, India-headquartered pharmaceutical company, has agreed to have a subsidiary of China Medical System Holdings (CMS), a specialty pharmaceutical company focused on sales and marketing in China, to develop and commercialize seven generic products in Mainland China.

Sun Pharma says the companies’ collaboration now covers eight generic products in total. In June 2019, Sun Pharma had announced a collaboration with CMS for two specialty products, tildrakizumab and cyclosporine A 0.09% eye drops, for the Greater China market.

Sun Pharma says the total addressable market size for all eight products is about $1 billion in Mainland China. Under the agreement, the initial term of agreement shall be 20 years from the first commercial sale of the respective products in Mainland China and may be extended for an additional three years as per mutual agreement of the two parties.

Source: Sun Pharmaceuticals

Europe

EMA Requests Name Change for Liposomal Drugs to Avoid Medication Errors

The European Medicines Agency (EMA) has requested all marketing authorization holders of medicines containing liposomal drug-delivery systems to submit a variation to change the names of these medicines before the end of September 2019.

The variation request was made following a number of reports of serious medication errors, some leading to death, and after a consultation with the EMA’s Committee for Medicinal Products for Human Use (CHMP) and the Coordination Group for Mutual Recognition and Decentralised Procedures-Human (CMDh).

The EMA said this recommendation was made jointly by the CHMP and the CMDh at their July meetings. The recommendation aims to make a clearer distinction between liposomal and non-liposomal formulations of the same active substance to avoid medication errors. The EMA notes that since the two formulations may have different biodistribution and release properties, medication errors can pose serious risks to the health of patients.

The EMA said so far, there has been no agreed approach to the naming of medicines containing liposomal or pegylated liposomal formulations. This recommendation is made to enable healthcare professionals and patients to better distinguish them from conventional non-liposomal medicines. This is a particular concern when electronic prescribing and dispensing tools are used, as in the absence of a more descriptive term for the liposomal medicines, they can be mixed up with non-liposomal medicines.

Source: European Medicines Agency

Swissmedic Publishes Updated Test Method for Nitrosamines in Sartan Medicines

The Swiss Agency for Therapeutic Products (Swissmedic), the national pharmaceutical regulatory agency of Switzerland, has upgraded its test method for sartans with a critical chemical structure for nitrosamines to prevent nitrosamine contamination in sartan-containing medicines.

The test method that was first published in mid-December 2018, has now been upgraded to determine whether the amounts of N-nitrosodimethylamine and N-nitrosodiethylamine contained in valsartan and related sartans are above or below the safety limit. The method is based on the use of gas chromatography—mass spectrometry.

Swissmedic says the updated test method is more robust and sensitive than the original one.

Swissmedic’s own lab, Official Medicines Control Laboratory, began testing sartans since sartan-containing medicines had to be recalled from the market in the summer and autumn of 2018 due to contamination.

Source: Swissmedic

India

Dr. Reddy’s Receives FDA Complete Response Letter

Dr. Reddy’s Laboratories has received a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) for its generic versions of Teva Pharmaceutical Industries’ Copaxone (glatiramer acetate), a drug for treating multiple sclerosis, and Merck & Co.’s Nuvaring (etonogestrel/ethinyl estradiol vaginal ring).

The company initially disclosed the CRL in an August 2019 investor presentation and said it was preparing responses. Dr. Reddy’s says it will continue to engage with the FDA to resolve outstanding concerns and focus on quality.

Source: Dr. Reddy’s

Emcure Receives FDA Warning Letter for Finished Pharmaceuticals Drug Mfg Facility

Emcure Pharmaceuticals, which develops, manufactures and markets pharmaceutical products, has received a Warning Letter from the US Food and Drug Administration (FDA) for GMP violations at its drug-manufacturing facility for finished pharmaceuticals in Maharashtra, India. The Warning Letter was issued following an inspection from February 11 to February 20, 2019.

Among the issues cited by the agency was not adequately investigating certain sterility failures obtained during routine batch release testing and lacking sufficient data in sterility-failure investigations. The agency said that although the company’s investigations substantially addressed the potential for microbial contamination during sterility testing, it deemphasized potential manufacturing causes.

The FDA noted that the company had rejected a portion (sub-lot) of each batch and released the remaining sub-lots for distribution to the United States. The FDA acknowledged, however, the firm’s decision to recall the distributed sub-lots after discussion with the FDA and the company’s decision to install a sterility test isolator. “We also acknowledge your commitment to conduct a further review of these failures and evaluate procedures for microbiological out-of­-specification investigations to ensure they provide appropriate details in documenting root cause as well as adequate impact assessments with respect to other lots (or sub-lots) that may be impacted,” said the FDA in its letter.

The FDA says in a previous inspection from August 7 to August 17, 2017, the agency was cited for similar cGMP observations in which the agency said Emcure inadequately performed microbiological investigations.

The FDA is requesting that the company provide several items, including: (1) an assessment of its overall system for investigations of deviations, atypical events, complaints, out-of-specification results, and failures; (2) a comprehensive, third-party evaluation of records relating to discrepancies, deviations, complaints, maintenance, detailed batch defect history, and investigations related to potential sealing variability and container-closure integrity issues; and (3) plans and procedures to ensure that future sterility-failure investigations include a comprehensive evaluation of potential vulnerabilities in the manufacturing operation,

Source: FDA

FDA Cites Natco Pharma’s API Mfg Facility in India

The US food and Drug Administration (FDA) has issued a Form 483 with six observations for Natco Pharma’s active pharmaceutical ingredient (API) manufacturing facility in Mekaguda Village, India, near Hyderabad.

The regulatory inspection was conducted during the period August 5, 2019 to August 9, 2019. In a filing with the Bombay Stock Exchange, Natco says the observations are mostly procedural in nature and are not related to data integrity and that all the observations can be addressed within a short period of time. 

A Form 483 by the FDA is issued to a firm at the conclusion of an inspection to notify the company’s management of objectionable conditions. At the conclusion of an inspection, the FDA Form 483 is presented and discussed with the company’s senior management. The agency says companies are then encouraged to respond to the Form 483 in writing with their corrective action plan and then to implement that action plan expeditiously.

Source: Natco Pharma

Israel

Mapi to Build New Sterile Injectable Mfg Facility for Generic of MS Drug Copaxone

Mapi Pharma, a late-stage clinical development biopharmaceutical company, has signed a lease agreement with the Har-Hotzvim Hi-Tech Park in Jerusalem, Israel to establish a new sterile production plant for glatiramer acetate depot injectable products for the treatment of patients with relapsing-remitting multiple sclerosis.

Mapi Pharma is engaged in the development of improved extended-release versions of existing commercially successful products. Its glatiramer acetate depot injectable product, a once-monthly injection, is a follow-on to Teva Pharmaceutical Industries’ daily 20-mg and the thrice-weekly 40-mg dosage of Copaxone (glatiramer acetate) for treating relapsing remitting multiple sclerosis and primary progressive multiple sclerosis.

The new leased area will be commissioned for a commercial-scale production facility for its glatiramer acetate depot injectable products. The nearly 50,000-square-foot plant was previously part of Omrix Biopharmaceuticals, a Johnson & Johnson Company and was an FDA-approved facility.

The new facility is partially funded by a grant of over $2.5 million received by Mapi in March 2019 from the Israeli Ministry of the Economy as part of an overall investment of approximately $14 million for equipment. The plant is located in a Zone A region, allowing tax and grants benefits. Mapi says its establishment will lead to the hiring of more employees with sales expected to be exported.

Mapi’s current production capacity includes a GMP-approved active pharmaceutical ingredient facility in Neot Hovav, Israel and a GMP-approved quality assurance laboratory in Ness Ziona, Israel.

In April 2018 Mapi Pharma partnered with Mylan in an agreement that granted Mylan an exclusive license to commercialize glatiramer acetate depot injection for relapsing multiple sclerosis. Under the term of the agreement, Mapi will supply glatiramer acetate depot to Mylan for commercial sale.

Source: Mapi Pharma

Kuwait

Mezzan Holding Acquires $69-Million- Stake in KSPICO, Kuwait’s Only Pharma Manufacturer

Mezzan Holding, a manufacturer and distributor of food, beverage, and healthcare products, has acquired a 67% stake in Kuwait Saudi Pharmaceutical Industries Company (KSPICO), a manufacturer of pharmaceutical products. The transaction value is KWD 21 million ($69 million).

Under the agreement, Mezzan will be granted majority board seats and the effective control of KSPICO.

Mezzan says this acquisition comes after its recent expansion into the healthcare space as it became the distributor of Medtronic’s and Covidien’s medical products and equipment in Kuwait through a joint venture agreement signed in June 2019.

Source: Mezzan

United States

Hikma Adds Nalaxone, Epinephrine Pipeline Products in Pact with Insys Therapeutics

Hikma Pharmaceuticals, a pharmaceutical technology company and supplier of generics, has agreed to acquire a complementary manufacturing platform and two pipeline products from Insys Therapeutics, a Chandler, Arizona-based pharmaceutical company specializing in cannabinoids and drug-delivery systems.

Hikma has agreed to acquire unit-dose nasal and sublingual spray manufacturing equipment as well as two pipeline products, naloxone 505 (b)2 nasal spray and epinephrine 505(b)2 nasal spray. Nalaxone is a medication used to block or reverse the effect of opioids. Epinephrine is a medication used to treat anaphylaxis, cardiac arrest, and superficial bleeding. The 505(b)(2) regulatory pathway under the US Food and Drug Administration is a type of new drug application submission that can be used to obtain the approval of a new drug that contains similar active ingredients to a previously approved drug and is used for changes in dosage form, strength, route of administration, formulation, dosing regimen, or new indication.

In June 2019, Insys filed petitions seeking relief under Chapter 11 of the US Bankruptcy Code. As part of this process, Insys initiated a court-supervised process to sell its assets. Hikma says this process has now concluded with respect to certain assets.

Source: Hikma Pharmaceuticals